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GastroPlus药代与制剂模拟软件:PBPK及ACAT模型

 

 

近年来,采用GastroPlus软件进行相关的科研工作越来越多,包括FDA在内的等单位已将GastroPlus的建模与模拟工作纳入日常化工作中。与此同时,大量高水平的文章也层出不穷。

凡默谷特挑选了涵盖法规部门、制药企业、学术单位的典型文章共12篇,内容涉及PBPKPK-PDDDIIVIVC、特殊人群PK预测等多个方面。每篇文献翻译了摘要,以便大家能快速地获取文章内容,希望这些信息能够为大家的科研工作带来一点帮助。

1. IVIVC应用】: 利培酮微球注射剂的IVIVC模型

In vitro-in vivo correlation of parenteral risperidone polymeric microspheres

Jie Shen,a Stephanie Choi,b Wen Qu,b Yan Wang,b and Diane J. Burgessa,J Control Release. 2015 Nov 28; 218: 2–12. (IF=7.786)

【摘要】 本研究的目的:确认处方组成相同但生产工艺不同的高分子微球利培酮是否能搭建体内外IVIVC模型。选择利培酮作为治疗模型,与上市药品Risperdal Consta® 有相似大小的聚乳酸-羟基乙酸共聚物(PLGA)作为微球材料。通过不同生产工艺的利培酮微球有相似的载药量(约37%),但理化性质明显不同,比如孔隙度、粒、粒径和粒径分布。利培酮微球体外溶出方法,采用不同的测试方法,比如用USP 4法。利培酮微球采用肌肉注射给药获得兔子的体内PK曲线;接着,把得到的PK曲线采用Loo–Riegelman方法进行去卷积,并将计算得到的体内释放与体外微球释放溶出进行对比;A级IVIVC得到了建立,并用组成相同的利培酮微球的体外释放数据进行验证,这些数据采用USP 4法检测得到;该IVIVCs 模型展现了很好的预测性及重复性。结果表明,USP 4法对处方组成相同,而生产工艺不同的利培酮PLGA微球有良好的区分能力,也可以预测被研究的动物药物体内行为。

2. 【DDI研究】:利用体外溶出渗透室定量预测pH依赖性药物药物相互作用与PBPK模型相比

Utilizing In Vitro Dissolution-Permeation Chamber for the Quantitative Prediction of pH-Dependent Drug-Drug Interactions with Acid-Reducing Agents: a Comparison with Physiologically Based Pharmacokinetic Modeling

Zhu A Z X, Ho M C D, Gemski C K, et al The AAPS journal, 2016, 18(6): 1512-1523. (IF=3.423)

【摘要】许多口服药物的溶解度具有pH依赖性,这与服用酸还原剂药物能够显著削弱药物的吸收和暴露一致。本文pH依赖性药物药物相互作用预测方法包括体外溶出渗透室、PBPK模型,通过定量的预测临床已知的具有pH依赖性药物药物相互的11个药物来评估这两方法的预测能力。溶出渗透室有胃肠道腔室组成,系统通过仿生膜进行分割,预测结果与临床结果一致,胃肠道腔室的AUC比例与临床结果具有较好的相关性(R=0.72,P=0.0056),系统房室的AUC比例与实测的临床Cmax有较强的相关性(R=0.91,P=0.0003)。PBPK模型也预测了这11个化合物,模拟结果表明预测结果与临床DDI实测结果有显著的相关性。今后,需要评估Z-factor基础PBPK模型预测pH依赖性DDI的预测能力。本文说明严重的pH依赖性DDI能够通过体外实验和计算机预测。

3. 【PK-PD研究】:建立生理药代动力学/药效动力学模型预测基因多态性对受体/转运体占据为代表的中枢神经系统药物的药代与药效行为影响

Pharmacodynamics Represented by Receptor/Transporter Occupancy of Central Nervous System Drugs

Saeed Alqahtani, Amal Kaddoumi. Clin Pharmacokinet. 2016 Aug;55(8):957-69.

【摘要】背景:基因多态性是导致个体间用药有效与安全变异的主要决定因素,同时也是当前临床实验和药物开发主要挑战之一。本工作的目的是建立生理药代动力学/药效动力学模型(PBPK/PD),预测伴随着基因多态性PK参数变化,以及这些改变后对药物PD作用的影响。
方法 本研究建立了喹硫平和氟伏沙明这两个作用于中枢神经系统药物的PBPK模型,这两个药物都是多态性代谢酶的底物,在该工作中将代谢酶活性以及丰度的相应变化都整合到了模型中。然后,将PBPK模型链接PD模型以预测这些改变对药物PD效应的影响。
结果 利用PBPK模型预测的药物PK差异与报道的临床数据较好吻合。另外,PBPK/PD模型能够表述药物的PD效应与脑部组织游离分数关系,以及预测受体/转运体占据百分比的变化,该数值来自伴随遗传变异的正电子发射断层摄影占位研究。结论 该工作提供一个简单的途径预测作用中枢神经系统药物受基因多态性影响的PK参数变化,以及伴随的PD效应改变。当然基因多态性对药物PD效应的影响还需要进一步体内数据进行验证。

4. 儿童人群用药】:采用基于生理的药动学模型模拟更昔洛韦及前药缬更昔洛韦在成人及儿童体内的药动学行为

A Physiologically Based Pharmacokinetic Model for Ganciclovir and Its Prodrug Valganciclovir in Adults and Children
Lukacova V, Goelzer P, Reddy M, et al The AAPS journal, 2016, 18(6): 1453-1463.(IF=3.423)

【摘要】基于生理的药动学模型PBPK已经用于开发更昔洛韦及前药缬更昔洛韦。基于药物的物理化学性质及体外的实测数据进行自底而上的模拟,这种方法在临床前不同动物种属间得到了验证,而临床模型在成人,儿童及新生儿患者体内得到逐步的验证。最终的模型考虑了缬更昔洛韦通过酯酶转化成更昔洛韦,并且在肠道,肝脏和肾脏中加入转运体考察在膜限速型组织中的分布。PBPK模型可以解释与年龄有关的组织体积,成分,血流速率,肾脏滤过清除等参数,可以很好地来拟合成人及儿童体内的血浆暴露曲线。总的来说,这项工作说明了PBPK模型的逐步发展,可以用来预测药物在婴儿及新生儿体内的PK行为,因此可以协助那些难以获得临床数据的敏感人群的药物开发。

5. 【生物等效性研究】:整合体外、建模、体内三种方法,研究华法林的生物等效性

Integrating In Vitro, Modeling, and In Vivo Approaches to Investigate Warfarin Bioequivalence

Zhang X, Wen H, Fan J, et al CPT: Pharmacometrics & Systems Pharmacology, 2017.

【摘要】我们采用建模与模拟的方法,探究华法林仿制药的生物等效性(BE)出现的隐患。为了检验我们的假设,即减少华法林包含物片中的异丙醇,减慢在酸性介质中的溶出,对华法林钠片在体内的药代动力学行为有显著的影响,我们构建了生理药动学及吸收模型进行建模与模拟,并采用制剂相关的参数和体外溶出相关的数据作为录入参数。参数敏感性分析表明, 华法林在体内的药代动力学对溶解度、颗粒大小、密度、在pH4.5介质中的溶出速率等参数不敏感,但pH6.8介质对其溶出速率和溶出能力影响较大。虚拟生物等效性试验表明,降解后的华法林钠片在pH4.5介质中的溶出速率较慢,但如降解后的药品在pH6.8介质中的溶出与未降解的溶出是相似的,则二者生物等效。采用双交叉设计、单剂量在健康受试者进行BE试验,以检测假设是否相同,并证实了模拟结论。本文中的降解片代表了典型家庭中将药品储存在浴室条件下(高温高湿)。

6. 【疾病人群(肾损伤)】:通过计算机模拟了解肾损伤对二甲双胍口服吸收的影响

Mechanistic understanding of the effect of renal impairment on metformin oral absorption using computer simulations

Almukainzi M, Gabr R, Abdelhamid G, et al.Journal of Pharmaceutical Investigation, 2017, 47(2): 151-161.

【摘要】与肾衰竭患者二甲双胍积累有关的生理参数尚未完全了解。在这些患者中,高肌酐浓度对二甲双胍的消除作用是未知的。本研究的目的是:(1)评估使用PBPK模型在预测健康和肾脏损伤个体中二甲双胍血药浓度的作用。(2)确定影响肾功能损伤患者体内药物浓度的参数。(3)通过假设存在对MATE1转运体的竞争性抑制,研究肌酐浓度与二甲双胍消除之间的相关性。所有的PBPK模拟都是使用 GastroPlus™完成。将都服用850毫克二甲双胍HCl的健康成人和肾衰竭患者的模拟数据与实验实测数据进行比较。为了研究肌酸浓度通过MATE1转运体对二甲双胍消除的影响,使用人胚肾细胞HEK293和MATE1过表达的HEK293细胞研究了0.35、0.5、1、2和5 mg / dl的肌酐对10µM二甲双胍消除的影响。我们的模型能够预测健康和肾衰竭患者的二甲双胍的吸收。肾功能损伤模型显示,肾和肝脏中MATE1转运体的下调是这些患者药物浓度增加的必要条件。然而,肾功能损害患者肌酐的积累未能与MATE1下调连接起来。了解二甲双胍血药浓度增加的原因有助于减少临床研究和对患者的副作用。

7. 【代谢酶与转运体】:采用高级隔室吸收与转运模型(ACAT)预测药物非线性肠道吸收中CYP3A与P-gp的相对重要性

The Prediction of the Relative Importance of CYP3A/P-gp to the Non-linear Intestinal Absorption of Drugs by Advanced Compartmental Absorption and Transit (ACAT) Model

Takano J, Maeda K, Bolger M B, et al.Drug Metabolism and Disposition, 2016: dmd. 116.070011.(IF=4.242)

【摘要】肠道内的CYP3A酶和P-gp蛋白能够降低底物药物在肠道内的吸收。由于CYP3A酶的底物特异性和P-gp蛋白的底物特异性经常有重合的情况,因此很难评估它们的饱和性;而且关于底物药物剂量依赖的FaFg(服用药物中到达门静脉的百分数)以及CYP3A酶和P-gp蛋白的相对的重要性在很多案例中并没有被清晰地阐明。

因此,我们尝试建立起一种通用的方法,能够基于体外的实验数据来预测几种CYP3A酶和/或P-gp蛋白底物的体内的吸收。其中一个关键的地方是通过设置放大因子(SF)来修正实测的体内清除与基于体外试验数据预测的清除之间的差异。此外同时优化了CYP3A酶和P-gp蛋白的Vmax的SF(SFCYP3A和SFP-gp)来,以解释CYP3A酶和/或P-gp蛋白底物药物的FaFg。当同时考虑SFCYP3A和SFP-gp时,可以实现FaFg最好的预测结果。而且模拟过程也阐明了CYP3A酶和P-gp蛋白在决定FaFg方面的相对重要性。

特别地,维拉帕米在肠道内的非线性吸收是由CYP3A酶的代谢饱和引起的,而奎尼丁的非线性吸收则同时取决于CYP3A酶和P-gp蛋白的反应饱和。此外,对于底物药物剂量依赖性的FaFg,无论是选择性的,还是同时存在CYP3A酶和/或P-gp蛋白的作用,模型都能够很好的预测。因此,我们建议可以采用优化SFCYP3A和SFP-gp后的数学模型来预测药物的FaFg,这种方法即便是在对体内代谢酶/转运体过程完全不清除的情况下,依然能够适用于由体外试验到体内吸收的外推预测。

8. 【食物效应研究】:采用生理性吸收模型探索食物与胃内pH的变化对艾乐替尼药动学的影响

Physiologically Based Absorption Modeling to Explore the Impact of Food and Gastric pH Changes on the Pharmacokinetics of Alectinib

Parrott N J, Li J Y, Takano R, et al.The AAPS journal, 2016, 18(6): 1464-1474.(IF=3.423)

【摘要】艾乐替尼,一种碱性脂蛋白,淋巴瘤激酶抑制剂,水溶性很低,已经获得FDA的批准,用于治疗ALK阳性非小细胞肺癌患者。本文阐述了在药品临床开发过程中基于生理的吸收模型来预测和理解食物与胃内pH值对艾乐替尼吸收的影响。GastroPlus软件整合药物基本的体外数据及拟合数据开发出吸收模型。将实测的静脉滴注数据来拟合药物的处置模型,并结合吸收模型与处置模型来模拟口服的药动学行为。模拟结果与临床数据进行比较,临床数据来源于食物效应研究以及药物药物相互作用研究(与埃索美拉唑的相互作用,埃索美拉唑是一种胃酸抑制剂)。尽管无法预测出食物效应影响的确切程度,但至少通过临床数据可以证实食物效应的阳性影响和几乎可以忽略的胃pH值得影响。采用临床的食物效应数据优化吸收模型,优化后的模型可进一步应用获得餐后给药时间的的建议。

生物制药吸收模型的应用是一个很有潜力的领域,可进一步简化后期药物开发,并对监管问题产生影响。

9. 【晶型研究】:采用机制性吸收模型模拟非晶型固体分散制剂

Physiologically Based Absorption Modeling for Amorphous Solid Dispersion Formulations

Mitra A, Zhu W, Kesisoglou F.Molecular pharmaceutics, 2016, 13(9): 3206-3215.(IF=4.440)

【摘要】固体分散体制剂通常被用于难溶性药物的开发。这种类型的制剂由于使得化合物有较高的溶解动力学以及增加了制剂的溶出速率,同时也是因为药物分子在制剂中是以一种高能量无定型状态存在,因而能够提高药物的生物利用度。在这篇文章中,我们阐述了生理吸收模型在机制性的理解固体分散体的临床药动学方面的应用。这里我们展示了3个案例,包括不同类型的固体分散体制剂在人体内的生物学行为,以及通过模型模拟对其体内行为进行回顾性的理解。

本文案例1中,随着剂量递增药物在体内具有线性PK,然后利用无定型的溶解度预测生物行为。案例2证明通过构建的模型,能够预测出随着剂量增加吸收的比例(%Fa)降低,进一步证明这种模型可以在吸收饱和存在的情况下,用于预测药物临床的体内行为。最后,案例3为了描述随着剂量递增临床中吸收不完全和较低的现象构建了一个吸收模型。这些案例证明了生理吸收模型在深入理解固体分散体在体内的行为,以及影响体内行为的关键因素方面的实用性,进而可以帮助设计高质量的药品,并最终使病人获益。

10. 【法规部门对待建模模拟态度】:先进的药品质量-综述US FDA药品质量办公室的科学与研究

Advancing pharmaceutical quality: An overview of science and research in the U.S. FDA’s Office of Pharmaceutical Quality

Fisher A C, Lee S L, Harris D P, et al.International journal of pharmaceutics, 2016, 515(1): 390-402.(IF= 3.649)

【摘要】失败一直围绕着药品质量,特别是关于药品生产问题以及设备修复,从而导致了在美国有大量的药品储存以及召回的事件。重要的科学进步促使了管理条例的建立,特别是在生物类似物、精准医疗、联合用药、新兴的制造技术以及使用大数据等方面。现在制药生产越来越全球化了,因此也促使对更加有效的监管体系的需求以检测药品的质量。此外,加快审查以及加速审批也让有限监管资源更加高效提供了驱动力。为处理这些监管挑战,FDA的药品审评与研究中心(CDER)的药品质量(OPQ)办公室构建了一套严格的科学与研究程序,以支持对药品质量审核、检查、监督、标准化以及政策开发等工作。科学与研究是对新药、仿制药、非处方药、生物制品包括生物类似物的质量风险评估的基础。这篇文章将综述OPQ科学与研究的一系列活动,以支持药品在北美市场用药安全、有效、高质量的使命。

11. 【Roche应用文章】:通过吸收模型与溶出试验表征Basmisanil,一种低溶解度速释制剂的释放特征。

Characterising Drug Release from Immediate-Release Formulations of a Poorly Soluble Compound, Basmisanil, Through Absorption Modelling and Dissolution Testing

Stillhart C, Parrott N J, Lindenberg M, et al.The AAPS journal, 2017, 19(3): 827-836.(IF=3.423)

【摘要】本次研究的目的在于通过机制性吸收模型,溶出试验以及拉曼光谱成像技术表征BCS II类药物Basmisanil的释放与吸收机制。GastroPlus软件中内建了吸收模型,并且用人体单剂量的PK数据进行了验证。通过生物体相关的溶出及拉曼光谱成像技术表征不同的口服Basmisanil制剂的性质及释放行为。最后,通过传统及机制性去卷积方式的对比,建立IVIVC模型。GastroPlus软件能够准确地模拟Basmisanil口服片剂及颗粒剂在体内的暴露数,低于200mg的口服剂量的吸收主要是溶出限速的,所以对制剂学的性质也特别敏感。

的确,120mg的薄膜包衣片的暴露数减少,在生物体介质中测定的溶出速率的减慢是因为药物载量的不同。拉曼光谱成像技术证实显示120mg该种制剂的渗流阈值,从而证实了该假设。具有生物相关性的溶解度在不同制剂之间可以很好地进行区分,并且可以用来搭建VIVC模型,该项研究表明了机制性吸收模型的适用性和影响力以及运用生物药剂学体外工具来合理地进行药物研发。

12. PBPK综述】:生理药代动力学模型(PBPK)在药物研发及监管中的研究

Physiologically-Based Pharmacokinetics in Drug Development and Regulatory Science

Malcolm Rowland, Carl Peck, and Geoffrey Tucker. (2011) Annu. Rev. Pharmacol. Toxicol. 51:45–73. (IF: 21.543)

【摘要】生理药代动力学模型(PBPK)在药物研发与监管中得到了广泛应用意味着新时代的来临,这反映了过去10年中,在利用人体外试验数据预测主要的药代动力学参数方面取得了重大进步,并且涌现了一批可获得到的专业软件平台与相关数据库。本文对如下内容进行综述:药物清除率、分布与吸收预测方面的进步与当前挑战,基于PK定量预测的药物药物相互作用(DDI)的程度,及预测年龄、遗传学、疾病与剂型的影响。这在选择和设计合适的临床研究方面具体很好的价值,这隐含了PBPK在资源节约方面具有意义,同时其整体观念将跨越临床前/临床方面药代动力学应用的鸿沟;最后,对PBPK在药物研发、审批示范与个体化用药实践的预期应用方面的定位进行阐述。

中国客户采用GastroPlus 软件发表的部分文献列表

英文文献:

001 PBPK modeling and simulation in drug research and development. IF=3.138
Zhuang X, Lu C. (2016) Acta Pharmaceutica Sinica B June 23

002 Virtual population pharmacokinetic using physiologically based pharmacokinetic model for evaluating bioequivalence of oral lacidipine formulations in dogs. IF=2.106
Yang B, Wu C, Ji B, Wu M, He Z, Shang L, Sun J. (2016) Asian J. Pharm. Sci. Mar 21
003
Application of physiologically based pharmacokinetic modeling in the prediction of pharmacokinetics of bicyclol controlled-release formulation in human. IF=3.35

Wang B, Liu Z, Li D, Yang S, Hu J, Chen H, Sheng L, Li Y. (2015) Eur J Pharm Sci. Jun 24

004 Preclinical pharmacokinetics of TPN729MA, a novel PDE5 inhibitor, and prediction of its human pharmacokinetics using a PBPK model. IF=2.912
Gao ZW Zhu YT, Yu MM, Zan B, Liu J, Zhang YF, Chen XY, Li XN, Zhong DF. (2015) Acta Pharmacol Sin. Dec; 36(12):1528-36.

005 Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model. IF=1.544

Zhu L, Yang J, Zhang Y, Wang Y, Zhang J, Zhao Y, Dong W. (2015) Korean J Physiol Pharmacol. Mar;19(2):99-104.
006 
Prediction of the pharmacokinetics and tissue distribution of levofloxacin in humans based on an extrapolated PBPK model. IF=1.68

Zhu L, Zhang Y, Yang J, Wang Y, Zhang J, Zhao Y, Dong W. (2015) Eur J Drug Metab Pharmacokinet. Mar10.

007 Characterization of preclinical in vitro and in vivo ADME properties and prediction of human PK using a physiologically-based pharmacokinetic model for YQA-14, a new dopamine D3 receptor antagonist candidate for treatment of drug addiction. IF=2.457

Liu F, Zhuang X, Yang C, Li Z, Xiong S, Zhang Z, Li J, Lu C, Zhang Z. (2014) Biopharm Drug Dispos. Mar19.

008 Elucidation of Arctigenin Pharmacokinetics After Intravenous and Oral Administrations in Rats:Integration of In Vitro and In Vivo Findings via Semi-mechanistic Pharmacokinetic Modeling. IF=3.819

Gao Q, Zhang Y, Wo S, Zuo Z. (2014) AAPS J. Oct. 2

009 Interspecies prediction of oral pharmacokinetics of different formulations from dogs to human:physiologically based pharmacokinetic modelling combined with biorelevant dissolution. IF=3.289

Wu C, Kou L, Ma P, Gao L, Li B, Li R, Luo C, Shentu J, Hea Z, Sun J. (2015) RSC Adv. 5:19844

010 Profiling Biopharmaceutical Deciding Properties of Absorption of Lansoprazole Enteric-Coated Tablets Using Gastrointestinal Simulation Technology. IF=3.99

Wu C, Sun L, Sun J, Yang Y, Ren C, Ai X, Lian H, He Z. (2013) Int J Pharm. Jun 24

011 Simulation of the pharmacokinetics of bisoprolol in healthy adults and patients with impaired renal function using whole-body physiologically based pharmacokinetic modeling. IF=3.166

Li GF, Wang K, Chen R, Zhao HR, Yang J, Zheng QS. (2012) Acta Pharmacol Sin. Oct. 22

中文文献与论文:

高向波,倪韶青,江周虹,申屠建中,余露山.用GastroPlus 构建茶碱的早产儿生理药代动力学模型研究[J].中国临床药理学杂志,第34 卷第5 期2018 年3 月( 总第259 期)

王晨,王立新,张斗胜,胡昌勤.国产注射用盐酸万古霉素的质量评价[J].中国抗生素杂志,2018年3月第43卷第3期

吴倩,史爱欣.生理药代动力学模型及其在妊娠妇女用药研究中的应用现状[J].中国临床药理学杂志,2017,33(21):2209-2211.

李丽,杨进波.基于生理的口服吸收模型在仿制药研发中的应用和趋势[J].中国临床药理学与治疗学,2017,22(09):961-965.

张凤妹,王建,李佳妮.国内外阿那曲唑片溶出曲线相似性评价及采用GastroPlus~(TM)建立体内外相关性模型的研究[J].中国现代应用药学,2017,34(09):1272-1276.

李丽,杨进波.基于生理的药代动力学模型在创新药临床研发中的应用进展[J].中国临床药理学杂志,2017,33(17):1728-1732.

李莉,李琬晴,李迎,高静,张慧,孙建绪,郑爱萍.不同粒径黄体酮的制备及评价[J].国际药学研究杂志,2017,44(06):609-615.

陈琳.白芷呋喃香豆素的体内外处置以及基于CYP酶的药物相互作用研究[D].中国人民解放军军事医学科学院,2017.硕博论文

孙晓迪,张伟,胡爽,刘建芳.国产硝苯地平缓释片的体外溶出度和虚拟生物等效性研究[J].中国药师,2017,20(05):791-794.

李佳妮.阿那曲唑及其片剂国家药品标准提高研究[D].浙江工业大学,2016. 硕博论文

汪难喜 翟学佳 朱超然 张新林 吕永宁. 头孢地尼在健康人体中生理药动学模型的建立与应用[J] 《中国药房》2016年 第35期

张伟.盐酸二甲双胍口服制剂的体外溶出及在比格犬体内的相对生物利用度研究[D].河北医科大学,2016.硕博论文

高广宇,梅丹宇,喻芳邻,余惟平,王汝涛,龚伟,梅兴国.新型抗脑卒中化合物TID-101自微乳制剂大鼠体内生物利用度研究[J].国际药学研究杂志,2016,43(04):731-735.

高广宇.TID-101自微乳化释药系统的研究[D].中国人民解放军军事医学科学院,2016. 硕博论文

许羚,李禄金,王鲲等. 新药早期临床试验中的定量药理学方法[J]. 中国新药杂质2015, 24(1): 52-58

李小东,陈悦,李煜,洪利娅.采用GastroPlus~(TM)软件评估甲磺酸多沙唑嗪缓释片的体内外溶出特征[J].中国现代应用药学,2016,33(01):71-75.

吴亮.应用生理药动学模型对甲氨蝶呤在儿童体内药动学的预测及验证[D].西南交通大学,2015.

于明明,高志伟,陈笑艳,钟大放.采用生理药动学模型预测抗肿瘤新药法米替尼在人体中的药动学[J].药学学报,2014,49(12):1684-1688.

潘瑞雪,高源,陈万里,李玉兰,胡昌勤.溶出度实验结合计算机模拟技术评价国产阿莫西林胶囊的生物等效性[J].药学学报,2014,49(08):1155-1161.

潘瑞雪,余方键,邹文博,胡昌勤.用GastroPlus软件模拟技术评价头孢地尼胶囊制剂的有效性[J].中国新药杂志,2014,23(13):1506-1513.

安佃云.磷酸川芎嗪渗透泵片应用GastroPlusTM软件的模拟及处方优化[D].山东中医药大学,2014.硕博论文

胡昌勤,潘瑞雪.溶出度试验评价/预测固体口服制剂生物等效性的研究进展[J].中国新药杂志,2014,23(01):44-51.

李桦,庄笑梅.药代动力学人体预测及其在新药研发中的应用[J].中国药理学与毒理学杂志,2013,27(04):611-615.

潘瑞雪.溶出度实验结合计算机模拟技术评价国产β-内酰胺类抗生素的生物等效性[D].中国食品药品检定研究院,2013.

姜伟明.GastroPlus~(TM)软件在药物模型构建、人体血浆清除率预测和临床试验处方设计中的应用[D].上海交通大学,2013.

胡昌勤.对抗生素药品评价性抽验基本思路与方法的思考[J].中国抗生素杂志,2013,38(01):1-11.

孙乐.基于BCS系统的insilico/invitro模型评价药物及制剂的BA/BE[D].沈阳药科大学,2013.

采用GastroPlus发表的部分文献

Utility of Physiologically Based Pharmacokinetic Absorption Modeling to Predict the Impact of Salt-to-Base Conversion on Prasugrel HCl Product Bioequivalence in the Presence of Proton Pump Inhibitors . 

Fan J, Zhang X, Zhao L.The AAPS Journal, 2017: 1-8

Integrating in vitro, modeling, and in vivo approaches to investigate warfarin bioequivalence .

Zhang X, Wen H, Fan J, et al.CPT: Pharmacometrics & Systems Pharmacology, 2017.

Exploring Canine-Human Differences in Product Performance. Part II: Use of Modeling and Simulation to Explore the Impact of Formulation on Ciprofloxacin In Vivo Absorption and Dissolution in Dogs .

Martinez M N, Mistry B, Lukacova V, et al. The AAPS journal, 2017, 19(3): 712-726.  

Physiologically based pharmacokinetic (PBPK) modeling of pharmaceutical nanoparticles .

Li M, Zou P, Tyner K, et al. The AAPS journal, 2017: 1-17. 

Report from the EMA workshop on qualification and reporting of physiologically based pharmacokinetic (PBPK) modeling and simulation .

Zhao P. CPT: pharmacometrics & systems pharmacology, 2017, 6(2): 71-72. 

Advancing pharmaceutical quality: An overview of science and research in the US FDA’s Office of Pharmaceutical Quality .

Fisher A C, Lee S L, Harris D P, et al. International journal of pharmaceutics, 2016, 515(1): 390-402. 

Application of Physiologically Based Absorption Modeling to Characterize the Pharmacokinetic Profiles of Oral Extended Release Methylphenidate Products in Adults .

Yang X, Duan J, Fisher J. PloS one, 2016, 11(10): e0164641.  

Physiologically based pharmacokinetic (PBPK) modeling of pharmaceutical nanoparticles .

Li M, Zou P, Tyner K, et al. The AAPS journal, 2017: 1-17. 

IMI–Oral biopharmaceutics tools project–Evaluation of bottom-up PBPK prediction success part 2: An introduction to the simulation exercise and overview of results .

Margolskee A, Darwich A S, Pepin X, et al. European Journal of Pharmaceutical Sciences, 2017, 96: 610-625.  

IMI–oral biopharmaceutics tools project–evaluation of bottom-up PBPK prediction success part 1: Characterisation of the OrBiTo database of compounds .

Margolskee A, Darwich A S, Pepin X, et al. European Journal of Pharmaceutical Sciences, 2017, 96: 598-609.  

IMI–Oral biopharmaceutics tools project–Evaluation of bottom-up PBPK prediction success part 3: Identifying gaps in system parameters by analysing In Silico performance across different compound classes .

Darwich A S, Margolskee A, Pepin X, et al.European Journal of Pharmaceutical Sciences, 2017, 96: 626-642.

The Use of In Vitro and In Silico Technologies for Predicting Human Pharmacology and Toxicology of Carfentanil .

Feasel M G. University of Maryland, Baltimore, 2017.

Prediction of Losartan-Active Carboxylic Acid Metabolite Exposure Following Losartan Administration Using Static and Physiologically Based Pharmacokinetic Models .

Nguyen H Q, Lin J, Kimoto E, et al. Journal of Pharmaceutical Sciences, 2017. 

Development and qualification of physiologically based pharmacokinetic models for drugs with atypical distribution behavior: A desipramine case study .

Samant T S, Lukacova V, Schmidt S. CPT: Pharmacometrics & Systems Pharmacology, 2017.

Biopharmaceutics data management system for anonymised data sharing and curation: First application with orbito IMI project .

Lacy-Jones K, Hayward P, Andrews S, et al. Computer Methods and Programs in Biomedicine, 2017, 140: 29-44.  

In silico-in vitro-in vivo studies of experimentally designed carvedilol loaded silk fibroin-casein nanoparticles using physiological based pharmacokinetic model .

Kumar S, Singh S K. International journal of biological macromolecules, 2017, 96: 403-420.

Forecasting oral absorption across biopharmaceutics classification system classes with physiologically based pharmacokinetic models .

Hansmann S, Darwich A, Margolskee A, et al. Journal of Pharmacy and Pharmacology, 2016, 68(12): 1501-1515.   

The prediction of the relative importance of CYP3A/P-gp to the non-linear intestinal absorption of drugs by advanced compartmental absorption and transit (ACAT) model .

Takano J, Maeda K, Bolger M B, et al. Drug Metabolism and Disposition, 2016: dmd. 116.070011. 

A Physiologically Based Pharmacokinetic Model for Ganciclovir and Its Prodrug Valganciclovir in Adults and Children.

Lukacova V, Goelzer P, Reddy M, et al. The AAPS journal, 2016, 18(6): 1453-1463.  

Bio–relevant characterisation of lipidic formulations and prediction of in vivo exposure.

Benito-Gallo P. University of Nottingham, 2017.

A cross-species translational pharmacokinetic-pharmacodynamic evaluation of core body temperature reduction by the TRPM8 blocker PF-05105679 .

Gosset J R, Beaumont K, Matsuura T, et al. European Journal of Pharmaceutical Sciences, 2017. 

Lipophilic salts of poorly soluble compounds to enable high-dose lipidic SEDDS formulations in drug discovery .

Morgen M, Saxena A, Chen X Q, et al. European Journal of Pharmaceutics and Biopharmaceutics, 2017, 117: 212-223. 

The impact of supersaturation level for oral absorption of BCS class IIb drugs, dipyridamole and ketoconazole, using in vivo predictive dissolution system: Gastrointestinal Simulator (GIS) .

Tsume Y, Matsui K, Searls A L, et al. European Journal of Pharmaceutical Sciences, 2017, 102: 126-139.   

Characterising Drug Release from Immediate-Release Formulations of a Poorly Soluble Compound, Basmisanil, Through Absorption Modelling and Dissolution Testing .

Stillhart C, Parrott N J, Lindenberg M, et al.  The AAPS journal, 2017, 19(3): 827-836.

Exploring Canine-Human Differences in Product Performance. Part II: Use of Modeling and Simulation to Explore the Impact of Formulation on Ciprofloxacin In Vivo Absorption and Dissolution in Dogs .

Martinez M N, Mistry B, Lukacova V, et al. The AAPS journal, 2017, 19(3): 712-726.  

In vitro and in silico characterisation of Tacrolimus released under biorelevant conditions .

Mercuri A, Wu S, Stranzinger S, et al. International journal of pharmaceutics, 2016, 515(1): 271-280.   

In vitro–in vivo–in silico simulation studies of anti-tubercular drugs doped with a self nanoemulsifying drug delivery system.

Hussain A, Singh S K, Singh N, et al. RSC Advances, 2016, 6(95): 93147-93161.  

Comparing Dog and Human Intestinal Fluids: Implications on Solubility and Biopharmaceutical Risk Assessment .

Walsh P L, Stellabott J, Nofsinger R, et al. AAPS PharmSciTech, 2017, 18(4): 1408-1416.  

Utilizing In Vitro Dissolution-Permeation Chamber for the Quantitative Prediction of pH-Dependent Drug-Drug Interactions with Acid-Reducing Agents: a Comparison with Physiologically Based Pharmacokinetic Modeling .

Zhu A Z X, Ho M C D, Gemski C K, et al. The AAPS journal, 2016, 18(6): 1512-1523.  

Using physiologically based pharmacokinetic (PBPK) modeling to evaluate the impact of pharmaceutical excipients on oral drug absorption: sensitivity analyses .

Chow E C Y, Talattof A, Tsakalozou E, et al. The AAPS journal, 2016, 18(6): 1500-1511.  

Development of in vitro in vivo correlation models for clopidogrel tablets to describe administration under fasting and fed conditions .

Savu S N, Silvestro L, Mircioiu C, et al. therapy, 2016, 11(16): 18. 

Exploring the Feasibility of Biowaiver Extension of BCS Class III Drugs with Site-Specific Absorption Using Gastrointestinal Simulation Technology .

Sun L, Sun J, He Z. European journal of drug metabolism and pharmacokinetics, 2017, 42(3): 471-487.   

Physiologically Based Absorption Modeling to Explore the Impact of Food and Gastric pH Changes on the Pharmacokinetics of Alectinib .

Parrott N J, Li J Y, Takano R, et al. The AAPS journal, 2016, 18(6): 1464-1474.  

Physiologically Based Absorption Modeling for Amorphous Solid Dispersion Formulations .

Mitra A, Zhu W, Kesisoglou F. Molecular pharmaceutics, 2016, 13(9): 3206-3215.

Justification of drug product dissolution rate and drug substance particle size specifications based on absorption PBPK modeling for Lesinurad immediate release tablets.

Pepin X J H, Flanagan T R, Holt D J, et al. Molecular pharmaceutics, 2016, 13(9): 3256-3269. 

Physiologically Based Absorption Modeling to Design Extended-Release Clinical Products for an Ester Prodrug .

Ding X, Day J S, Sperry D C.  The AAPS journal, 2016, 18(6): 1424-1438.

Development of long-circulating docetaxel loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nanoparticles: optimization, pharmacokinetic, cytotoxicity and in vivo assessments .

Vardhan H, Mittal P, Adena S K R, et al. International Journal of Biological Macromolecules, 2017. 

Studies on Core-Shell Nanocapsules of Felodipine: In Vitro-In Vivo Evaluations .

Geroge J K, Verma P R P, Venkatesan J, et al. AAPS PharmSciTech, 2017: 1-18. 

In vitro and in vivo evaluation of gastro-retentive carvedilol loaded chitosan beads using Gastroplus™ .

Praveen R, Verma P R P, Venkatesan J, et al.  International Journal of Biological Macromolecules, 2017, 102: 642-650.

Integrating in vitro, modeling, and in vivo approaches to investigate warfarin bioequivalence .

 Zhang X, Wen H, Fan J, et al. CPT: Pharmacometrics & Systems Pharmacology, 2017.

Characterising Drug Release from Immediate-Release Formulations of a Poorly Soluble Compound, Basmisanil, Through Absorption Modelling and Dissolution Testing.

Stillhart C, Parrott N J, Lindenberg M, et al. The AAPS journal, 2017, 19(3): 827-836.  

In vitro dissolution models for the prediction of in vivo performance of an oral mesoporous silica formulation .

McCarthy C A, Faisal W, O'shea J P, et al. Journal of Controlled Release, 2017, 250: 86-95. 

In vitro–in vivo correlations: general concepts, methodologies and regulatory applications .

González-García I, Mangas-Sanjuán V, Merino-Sanjuán M, et al. Drug development and industrial pharmacy, 2015, 41(12): 1935-1947. 

Development and qualification of physiologically based pharmacokinetic models for drugs with atypical distribution behavior: A desipramine case study .

Samant T S, Lukacova V, Schmidt S. CPT: Pharmacometrics & Systems Pharmacology, 2017.

Identification and characterisation of a salt form of Danirixin with reduced pharmacokinetic variability in patient populations .

Bloomer J C, Ambery C, Miller B E, et al. European Journal of Pharmaceutics and Biopharmaceutics, 2017, 117: 224-231.

Mechanistic understanding of the effect of renal impairment on metformin oral absorption using computer simulations .

Almukainzi M, Gabr R, Abdelhamid G, et al. Journal of Pharmaceutical Investigation, 2017, 47(2): 151-161.

Application of Physiologically Based Absorption Modeling to Characterize the Pharmacokinetic Profiles of Oral Extended Release Methylphenidate Products in Adults .

Yang X, Duan J, Fisher J. PloS one, 2016, 11(10): e0164641. 

A Physiologically Based Pharmacokinetic Model for Ganciclovir and Its Prodrug Valganciclovir in Adults and Children.

Lukacova V, Goelzer P, Reddy M, et al. The AAPS journal, 2016, 18(6): 1453-1463.  

A strategy for early-risk predictions of clinical drug–drug interactions involving the GastroPlusTM DDI module for time-dependent CYP inhibitors .

Sohlenius-Sternbeck A K, Meyerson G, Hagbjörk A L, et al. Xenobiotica, 2017: 1-9. 

Influence of different proton pump inhibitors on the pharmacokinetics of voriconazole .

Qi F, Zhu L, Li N, et al. International Journal of Antimicrobial Agents, 2017, 49(4): 403-409.

Progress in Prediction and Interpretation of Clinically Relevant Metabolic Drug-Drug Interactions: a Minireview Illustrating Recent Developments and Current Opportunities .

Fowler S, Morcos P N, Cleary Y, et al. Current Pharmacology Reports, 2017, 3(1): 36-49.

Prediction of pharmacokinetics and drug-drug interaction potential using physiologically based pharmacokinetic (PBPK) modeling approach: A case study of caffeine and ciprofloxacin .

Park M H, Shin S H, Byeon J J, et al. The Korean Journal of Physiology & Pharmacology, 2017, 21(1): 107-115.    

Utilizing In Vitro Dissolution-Permeation Chamber for the Quantitative Prediction of pH-Dependent Drug-Drug Interactions with Acid-Reducing Agents: a Comparison with Physiologically Based Pharmacokinetic Modeling.

Zhu A Z X, Ho M C D, Gemski C K, et al. The AAPS journal, 2016, 18(6): 1512-1523.  

Food effects in paediatric medicines development for products Co-administered with food .

Batchelor H, Kaukonen A M, Klein S, et al. International Journal of Pharmaceutics, 2017.

Food Effect on Oral Bioavailability: Old and New Questions .

Yan J H. Clinical Pharmacology in Drug Development, 2017. 

Mechanistic prediction of food effects for Compound A tablet using PBPK model .

Li X, Shi L, Tang X, et al. Saudi journal of biological sciences, 2017, 24(3): 603-609. 

Mechanistic investigation of the negative food effect of modified release zolpidem .

Andreas C J, Pepin X, Markopoulos C, et al. European Journal of Pharmaceutical Sciences, 2017, 102: 284-298. 

Food effect: The combined effect of media pH and viscosity on the gastrointestinal absorption of ciprofloxacin tablet .

Radwan A, Zaid A N, Jaradat N, et al.European Journal of Pharmaceutical Sciences, 2017, 101: 100-106.  

Physiologically Based Absorption Modeling to Explore the Impact of Food and Gastric pH Changes on the Pharmacokinetics of Alectinib .

Parrott N J, Li J Y, Takano R, et al. The AAPS journal, 2016, 18(6): 1464-1474.  

Prediction of Losartan-Active Carboxylic Acid Metabolite Exposure Following Losartan Administration Using Static and Physiologically Based Pharmacokinetic Models .

Nguyen H Q, Lin J, Kimoto E, et al. Journal of Pharmaceutical Sciences, 2017. 

Exploring and validating physicochemical properties of mangiferin through GastroPlus® software .

Khurana R K, Kaur R, Kaur M, et al. Future Sci OA. 2017 Jan 16;3(1)

A cross-species translational pharmacokinetic-pharmacodynamic evaluation of core body temperature reduction by the TRPM8 blocker PF-05105679 .

Gosset J R, Beaumont K, Matsuura T, et al. European Journal of Pharmaceutical Sciences, 2017. 

Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays .

Lee J B, Zgair A, Taha D A, et al. European Journal of Pharmaceutics and Biopharmaceutics, 2017, 114: 38-42.  

In Vitro Evaluation of Absorption Characteristics of Peramivir for Oral Delivery .

Li Y, Wang Z, Li X, et al.  European journal of drug metabolism and pharmacokinetics, 2016: 1-9. 

Predicting exposure after oral inhalation of the selective glucocorticoid receptor modulator, AZD5423, based on dose, deposition pattern, and mechanistic modeling of pulmonary disposition.

Bäckman P, Tehler U, Olsson B. Journal of aerosol medicine and pulmonary drug delivery, 2017, 30(2): 108-117.  

PEGylated cyclodextrins as novel siRNA nanosystems: correlations between polyethylene glycol length and nanoparticle stability .

Godinho B M D C, Ogier J R, Quinlan A, et al. International journal of pharmaceutics, 2014, 473(1): 105-112.   

An in vitro and in silico study of the impact of engineered surface modifications on drug detachment from model carriers .

Wu S, Zellnitz S, Mercuri A, et al. International journal of pharmaceutics, 2016, 513(1): 109-117.

In vitro and in silico investigation of electrospun terbinafine hydrochloride-loaded buccal nanofibrous sheets .

Szabó P, Daróczi T B, Tóth G, et al. Journal of pharmaceutical and biomedical analysis, 2016, 131: 156-159.    

Characterization of pharmacokinetics in the Göttingen Minipig with reference human drugs: an in vitro and in vivo approach.

Lignet F, Sherbetjian E, Kratochwil N, et al. Pharmaceutical research, 2016, 33(10): 2565-2579.  

Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose.

Sachiko Fukui a,*, Hideki Yano a, Shuichi Yada a, et al.ASIAN journal of pharmaceutical sciences 12 (2017) 149–156

Gastrointestinal behavior and ADME phenomena: II. In silico simulation.
Lamberti G, Cascone S, Marra F, Titomanlio G, d’Amore M, Barba AA. (2016) J Drug Del. Sci. and Tech. 35:165
Folate-targeted amphiphilic cyclodextrin.siRNA nanoparticles for prostate cancer therapy exhibit PSMA mediated uptake, therapeutic gene silencing in vitro and prolonged circulation in vivo.
Evans JC, Malhotra M, Guo J, O'Shea JP, Hanrahan K, O'Neill A, Landry W, Griffin BT, Darcy R, Watson RW, O'Driscoll CM. (2016) Nanomedicine. Jul 4
Physiologically Based Absorption Modeling to Design Extended-Release Clinical Products for an Ester Prodrug.
Ding X, Day JS, Sperry DC. (2016) AAPS J. Jul 12
Evaluation of the GastroPlus™ Advanced Compartmental and Transit (ACAT) Model in Early Discovery.
Gobeau N, Stringer R, De Buck S, Tuntland T, Faller B. (2016) Pharm Res. Jun 8
Development of In Vitro In Vivo Correlation Models for Clopidogrel Tablets to Describe Administration Under Fasting and Fed Conditions.
Savu SN, Silvestro L, Mircioiu C, Anuta V. (2016) Farmacia 64(2):302-312
Use of physiologically relevant biopharmaceutics tools within the pharmaceutical industry and in regulatory sciences: Where are we now and what are the gaps?
Flanagan T, Van Peer A, Lindahl A. (2016) Eur J Pharm Sci. 91:84-90
Pore blocking: An innovative formulation strategy for the design of alcohol resistant multi-particulate dosage forms.
Schrank S, Jedinger N, Wu S, Piller M, Roblegg E. (2016) Int J Pharm. 509(1-2):219-28
PBPK modeling and simulation in drug research and development.
Zhuang X, Lu C. (2016) Acta Pharmaceutica Sinica B June 23
Toward Biopredictive Dissolution for Enteric Coated Dosage Forms.
Al-Gousous J, Amidon GL, Langguth P. (2016) Mol Pharm. May 10
Comparative human in-vivo study of an immediate release tablet over-encapsulated by gelatin and hydroxypropyl methyl cellulose capsules – impact of dissolution rate on bioequivalence.
Stegemann S, Vishwanath S, Kumar R, Cade D, Lowery M, Hutchison K, Michael Morgen M, Goodwin A, Lee C. (2016) Capsugel white paper
Integration of Life-Stage Physiologically-Based Pharmacokinetic (PBPK) Models with Adverse Outcome Pathways (AOPs) and Environmental Exposure Models to Screen for Environmental Hazards.
El-Masri H, Kleinstreuer N, Hines RN, Adams L, Tal T, Isaacs K, Wetmore BA, Tan YM. (2016) Toxicol Sci. May 4
Using Physiologically Based Pharmacokinetic (PBPK) Modelling to Gain Insights into the Effect of Physiological Factors on Oral Absorption in Paediatric Populations.
Villiger A, Stillhart C, Parrott N, Kuentz M. (2016) AAPS J. Apr 8
Use of Modeling and Simulation Tools for Understanding the Impact of Formulation on the Absorption of a Low Solubility Compound: Ciprofloxacin.
Martinez M, Mistry B, Lukacova V, Polli J, Hoag S, Dowling T, Kona R, Fahmy R. AAPS J. Apr 26
The solubility-permeability interplay and oral drug formulation design: Two heads are better than one.
Dahan A, Beig A, Lindley D, Miller JM. (2016) Adv Drug Deliv Rev. Apr 26
In vivo in silico pharmacokinetic simulation studies of carvedilol-loaded nanocapsules using GastroPlus™.
George JK, Singh SK, Verma P. (2016) Ther Deliv. May;7(5):305-18.
Virtual population pharmacokinetic using physiologically based pharmacokinetic model for evaluating bioequivalence of oral lacidipine formulations in dogs.
Yang B, Wu C, Ji B, Wu M, He Z, Shang L, Sun J. (2016) Asian J. Pharm. Sci. Mar 21
Simulated rat intestinal fluid improves oral exposure prediction for poorly soluble compounds over a wide dose range.
Berghausen J, Seiler FH, Gobeau N, Faller B. (2016) 4(1):35-53
Development of a Physiologically Based Pharmacokinetic/Pharmacodynamic Model to Predict the Impact of Genetic Polymorphisms on the Pharmacokinetics and Pharmacodynamics Represented by Receptor/Transporter Occupancy of Central Nervous System Drugs.
Alqahtani S, Kaddoumi A. (2016) Clin Pharmacokinet. Feb 25
In silico modeling of gastrointestinal drug absorption: predictive performance of three physiologically based absorption models.
Sjögren E, Thörn H, Tannergren C. (2016) Mol Pharm. Feb 29.
Physiologically-Based Pharmacokinetic Modeling in Pediatric Oncology Drug Development.
Rioux N, Waters NJ. (2016) Drug Metab Dispos. Mar 2
Pharmacokinetic evaluation of cefdinir-loaded floating alginate beads in rabbits using LC–MS/MS.
Praveen R, Singh SK, Verma PRP. (2016) J. Pharm. Investigation Mar 5
Clinical Micro-Dose Studies to Explore the Human Pharmacokinetics of Four Selective Inhibitors of Human Nav1.7 Voltage-Dependent Sodium Channels.
Jones HM, Butt RP, Webster RW, Gurrell I, Dzygiel P, Flanagan N, Fraier D, Hay T, Iavarone LE, Luckwell J, Pearce H, Phipps A, Segelbacher J, Speed B, Beaumont K. (2016) Clin Pharmacokinet. Feb 19.
Application of in vitro transmucosal permeability, dose number, and maximum absorbable dose for biopharmaceutics assessment during early drug development for intraoral delivery.
Yang Z, Sotthivirat S, Wu Y, Lalloo A, Nissley B, Manser K, Li H. (2016) Int J Pharm. Feb 20
LC-ESI-MS/MS estimation of loratadine-loaded Self-nanoemulsifying drug delivery systems in rat plasma: pharmacokinetic evaluation and computer simulations by GastroPlus™.
Verma S, Singh SK. (2016) J Pharm Biomedical Anal Feb. 8
Estimating Margin of Exposure to Thyroid Peroxidase Inhibitors Using High-throughput In Vitro Data, High-throughput Exposure Modeling, and Physiologically-Based Pharmacokinetic/Pharmacodynamic Modeling.
Leonard JA, Tan YM, Gilbert M, Isaacs K, El-Masri H. (2016) Toxicol Sci. Feb 10.
Physiologically Based Absorption Modeling to Impact Biopharmaceutics and Formulation Strategies in Drug Development—Industry Case Studies.
Kesisoglou F, Chung J, van Asperen J, Heimbach T. (2016) J Pharm Sci Jan. 23
Disease specific modeling: simulation of the pharmacokinetics of meloxicam and ibuprofen in disease state vs. healthy conditions.
Almukainzi M, Jamali F, Aghazadeh-Habashi A, Löbenberg R. (2016) Eur. J. Pharm. Biopharm. Jan. 2
Absorption, distribution, metabolism, excretion, and kinetics of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)proprionic acid ammonium salt following a single dose in rat, mouse, and cynomolgus monkey.
Gannon SA, Fasano WJ, Mawn MP, Nabb DL, Buck RC, Buxton LW, Jepson GW, Frame SR. (2015) Toxicology. Dec 29.
Solidified SNEDDS of loratadine: formulation using hydrophilic and hydrophobic grades of Aerosil®, pharmacokinetic evaluations and in vivo–in silico predictions using GastroPlus™.
Verma S, Singh SK, Verma PRP. (2016) RSC Adv. 6:3099-3116
Development of a Unified Dissolution and Precipitation Model and Its Use for the Prediction of Oral Drug Absorption.
Jakubiak P, Wagner B, Grimm HP, Petrig-Schaffland J, Schuler F, Alvarez-Sánchez R. (2016) Mol Pharm. Jan 5.
Methodology of oral formulation selection in the pharmaceutical industry.
Kuentz M, Holm R, Elder DP. (2015) Eur J Pharm Sci. Dec 11
Establishment of physiologically based pharmacokinetic model of atorvastatin.
Liu J-B, Zhu L-Q, Zhang Y, Yang J-W. (2015) Chinese J Hospital Pharmacy 35(16):1465-1469
Investigating the effect of autoinduction in cynomolgus monkeys of a novel anticancer MDM2 antagonist, idasanutlin, and relevance to humans.
Glenn KJ, Yu LJ, Reddy MB, Fretland AJ, Parrott N, Hussain S, Palacios M, Vazvaei F, Zhi J, Tuerck D. (2015) Xenobiotica. Nov 19:1-10.
Preclinical pharmacokinetics of TPN729MA, a novel PDE5 inhibitor, and prediction of its human pharmacokinetics using a PBPK model.
Gao ZW Zhu YT, Yu MM, Zan B, Liu J, Zhang YF, Chen XY, Li XN, Zhong DF. (2015)Acta Pharmacol Sin. Dec;36(12):1528-36.
Deciphering nifedipine in vivo delivery from modified release dosage forms: Identification of food effect.
Ilic M, Kovacevic I, Parojcic J. (2015) Acta Pharm. 65:427
In vitro anticancer properties and biological evaluation of novel natural alkaloid jerantinine B.
Qazzaz ME, Raja VJ, Lim KH, Kam TS, Lee JB, Gershkovich P, Bradshaw TD. (2015) Cancer Lett. Oct 26.
Mathematical Model-Based Accelerated Development of Extended-release Metformin Hydrochloride Tablet Formulation.
Chen W, Desai D, Good D, Crison J, Timmins P, Paruchuri S, Wang J, Ha K. (2015) AAPS PharmSciTech Oct. 19
Mitigation of Adverse Clinical Events of a Narrow Target Therapeutic Index Compound through Modified Release Formulation Design: An In Vitro, In Vivo, In Silico, and Clinical Pharmacokinetic Analysis.
Good DJ, Hartley R, Mathias N, Crison J, Tirucherai G, Timmins P, Hussain M, Haddadin R, Koo O, Nikfar F, Fung NK. (2015) Mol Pharm. Nov 4
Absorption, Metabolism, Excretion, and the Contribution of Intestinal Metabolism to the Oral Disposition of [14C]Cobimetinib, a MEK Inhibitor, in Humans.
Takahashi RH, Choo EF, Ma S, Wong S, Halladay J, Deng A, Rooney I, Gates M, Hop CE, Khojasteh SC, Dresser M, Musib L. (2015) Drug Metab Dispos. Oct. 8
Utility of PBPK Absorption Modeling to Guide Modified Release Formulation Development of Gaboxadol, a Highly Soluble Compound with Region-Dependent Absorption.
Kesisoglou F, Balakrishnan A, Manser K. (2015) J Pharm Sci. Oct 12.
Quantitative aspects of drug permeation across in vitro and in vivo barriers.
Krämer SD. (2015) Eur J Pharm Sci. Oct 19.
Development of Physiologically Based Pharmacokinetic/Pharmacodynamic Model for Indomethacin Disposition in Pregnancy.
Alqahtani S, Kaddoumi A. (2015) PLoS One. Oct 2;10(10)
Solidified SNEDDS of loratadine: Formulation using hydrophilic and hydrophobic grades of Aerosil®, pharmacokinetic evaluations and in vivo-in silico predictions using GastroPlus.
Verma S, Kumar Singh S, Verma PRP (2015) RSC Adv. Dec. 4
In vitro-in vivo correlation of parenteral risperidone polymeric microspheres.
Shen J, Choi S, Qu W, Wang Y, Burgess DJ. (2015) J Control Release. Sep 28;218:2-12.
Physicochemical and Pharmacokinetic Characterization of Amorphous Solid Dispersion of Meloxicam with Enhanced Dissolution Property and Storage Stability.
Ochi M, Kimura K, Kanda A, Kawachi T, Matsuda A, Yuminoki K, Hashimoto N. (2015) AAPS PharmSciTech Oct 5
A canine biorelevant dissolution method for predicting in vivo performance of orally administered sustained release matrix tablets.
Walsh PL, Bothe JR, Bhardwaj S, Hu M, Nofsinger R, Xia B, Persak S, Pennington J, Bak A. (2015) Drug Dev Ind Pharm. Sep 4:1-9
Effects of Cytochrome P450 3A4 Inhibitors - Ketoconazole and Erythromycin - on Bitopertin Pharmacokinetics and Comparison with Physiologically Based Modelling Predictions.
Boetsch C, Parrott N, Fowler S, Poirier A, Hainzl D, Banken L, Martin-Facklam M, Hofmann C. (2015) Clin Pharmacokinet. Sep 4.
Development of a Physiologically Based Pharmacokinetic/Pharmacodynamic Model to Identify Mechanisms Contributing to Entacapone Low Bioavailability.
Alqahtani S, Kaddoumi A. (2015) Biopharm Drug Dispos. Aug 21
Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A systematic review of published models, applications and model verification.
Sager JE, Yu J, Raguenau-Majlessi I, Isoherranen N. (2015) Drug Metab Dispos. Aug 21.
Comparison of Deconvolution-Based and Absorption Modeling IVIVC for Extended Release Formulations of a BCS III Drug Development Candidate.
Kesisoglou F, Xia B, Agrawal NG. (2015) AAPS J. Aug 20.
PEGylated y-tocotrienol isomer of vitamin E: Synthesis, characterization, in vitro cytotoxicity, and oral bioavailability.
Abu-Fayyad A, Behery F, Sallam A, Alqahtani S, Ebrahim H, El Sayed KA, Kaddoumi A, Sylvester PW, Carroll JL, Cardelli JA, Nazzal S. (2015) Eur J Pharm Biopharm. Jul 30. pii: S0939-6411(15)00325-2
Lipidic dispersion to reduce food dependent oral bioavailability of fenofibrate: In vitro, in vivo and in silico assessments.
O'Shea JP, Faisal W, Ruane-O'Hora T, Devine KJ, Kostewicz ES, O'Driscoll CM, Griffin BT. (2015) Eur J Pharm Biopharm. Jul 26. pii: S0939-6411(15)00303-3
pH-Dependent Solubility and Dissolution Behavior of Carvedilol-Case Example of a Weakly Basic BCS Class II Drug.
Hamed R, Awadallah A, Sunoqrot S, Tarawneh O, Nazzal S, AlBaraghthi T, Al Sayyad J, Abbas A. (2015) AAPS PharmSciTech. Jul 23
A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria.
Phillips MA, Lotharius J, Marsh K, White J, Dayan A, White KL, Njoroge JW, E Mazouni F, Lao Y, Kokkonda S, Tomchick DR, Deng X, Laird T, Bhatia SN, March S, Ng CL, Fidock DA, Wittlin S, Lafuente-Monasterio M, Benito FJ, Alonso LM, Martinez MS, Jimenez-Diaz MB, Bazaga SF, Angulo-Barturen I, Haselden JN, Louttit J, Cui Y, Sridhar A, Zeeman AM, Kocken C, Sauerwein R, Dechering K, Avery VM, Duffy S, Delves M, Sinden R, Ruecker A, Wickham KS, Rochford R, Gahagen J, Iyer L, Riccio E, Mirsalis J, Bathhurst I, Rueckle T, Ding X, Campo B, Leroy D, Rogers MJ, Rathod PK, Burrows JN, Charman SA. (2015) Sci Transl Med. Jul 15;7(296):296ra111
Assessment of In Vivo Clinical Product Performance of a Weak Basic Drug by Integration of In Vitro Dissolution Tests and Physiologically Based Absorption Modeling.
Ding X, Gueorguieva I, Wesley JA, Burns LJ, Coutant CA. (2015) AAPS J. Jul 1.
Acute toxicity prediction in multiple species by leveraging mechanistic ToxCast mitochondrial inhibition data and simulation of oral bioavailability.
Bhhatarai B, Wilson DM, Bartels MJ, Chaudhuri S, Price PS, Carney EW. (2015) Toxicol Sci. Jul 2.
In vitro-in vivo correlations: general concepts, methodologies and regulatory applications.
González-García I, Mangas-Sanjuán V, Merino-Sanjuán M, Bermejo M. (2015) Drug Dev Ind Pharm. Jul 2:1-13.
Pharmacometric Models for Characterizing the Pharmacokinetics of Orally Inhaled Drugs.
Borghardt JM, Weber B, Staab A, Kloft C. (2015) AAPS J. Jul;17(4):853-70
Preclinical pharmacokinetic studies of 3-deazaneplanocin A, a potent epigenetic anticancer agent, and its human pharmacokinetic prediction using GastroPlus™.
Sun F, Lee L, Zhang Z, Wang X, Yu Q, Duan X, Chan E. (2015) Eur J Pharm Sci. Jun 25.
Application of physiologically based pharmacokinetic modeling in the prediction of pharmacokinetics of bicyclol controlled-release formulation in human.
Wang B, Liu Z, Li D, Yang S, Hu J, Chen H, Sheng L, Li Y. (2015) Eur J Pharm Sci. Jun 24 - See more at: http://www.simulations-plus.com/publication.aspx?pID=11#sthash.10kckxY3.dpuf

Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

Kesisoglou F, Mitra A. (2015) AAPS J. May 22.
Development and validation of in vitro-in vivo correlation (IVIVC) for estradiol transdermal drug delivery systems.
Yang Y, Manda P, Pavurala N, Khan MA, Krishnaiah YS. (2015) J Control Release. May 13;210:58-66.
Application of Physiologically Based Absorption Modeling for Amphetamine Salts Drug Products in Generic Drug Evaluation.
Babiskin AH, Zhang X. (2015) J Pharm Sci. May 13.
Prediction of pH dependent absorption using in vitro, in silico, and in vivo rat models: Early liability assessment during lead optimization.
Saxena A, Shah D, Padmanabhan S, Gautam SS, Chowan GS, Mandlekar S, Desikan S. (2015) Eur J Pharm Sci. May 8;76:173-180
In vitro dissolution methodology, mini-Gastrointestinal Simulator (mGIS), predicts better in vivo dissolution of a weak base drug, dasatinib.
Tsume Y, Takeuchi S, Matsui K, Amidon GE, Amidon GL. (2015) Eur J Pharm Sci. May 12;76:203-212.
Prediction of the pharmacokinetics and tissue distribution of levofloxacin in humans based on an extrapolated PBPK model.
Zhu L, Zhang Y, Yang J, Wang Y, Zhang J, Zhao Y, Dong W. (2015) Eur J Drug Metab Pharmacokinet. Mar 10.
Pharmacometric Models for Characterizing the Pharmacokinetics of Orally Inhaled Drugs.
Borghardt JM, Weber B, Staab A, Kloft C. (2015) AAPS J. Apr 7
Food Effect in Humans: Predicting the Risk Through In Vitro Dissolution and In Vivo Pharmacokinetic Models.

Mathias N, Xu Y, Vig B, Kestur U, Saari A, Crison J, Desai D, Vanarase A, Hussain M. (2015) AAPS J. May 2

Prospective Predictions of Human Pharmacokinetics for Eighteen Compounds.

Zhang T, Heimbach T, Lin W, Zhang J, He H. (2015) J Pharm Sci. Feb 17.
Role of Self-Association and Supersaturation in Oral Absorption of a Poorly Soluble Weakly Basic Drug.
Narang AS, Badawy S, Ye Q, Patel D, Vincent M, Raghavan K, Huang Y, Yamniuk A, Vig B, Crison J, Derbin G, Xu Y, Ramirez A, Galella M, Rinaldi FA. (2015) Pharm Res. Feb 28.
Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model.
Zhu L, Yang J, Zhang Y, Wang Y, Zhang J, Zhao Y, Dong W. (2015) Korean J Physiol Pharmacol. Mar;19(2):99-104.
Development of a Novel Oral Cavity Compartmental Absorption and Transit Model for Sublingual Administration: Illustration with Zolpidem.
Xia B, Yang Z, Zhou H, Lukacova V, Zhu W, Milewski M, Kesisoglou F. (2015) AAPS J. Feb 26.
Comparison of biorelevant simulated media mimicking the intestinal environment to assess the solubility profiles of poorly soluble drugs.
Prasad D, Gu CH, Kuldipkumar A. (2015) Pharm Dev Technol. Feb 23:1-7
Interspecies prediction of oral pharmacokinetics of different formulations from dogs to human: physiologically based pharmacokinetic modelling combined with biorelevant dissolution.
Wu C, Kou L, Ma P, Gao L, Li B, Li R, Luo C, Shentu J, Hea Z, Sun J. (2015) RSC Adv. 5:19844
Utilizing Physiologically Based Pharmacokinetic Modeling to Inform Formulation and Clinical Development for a Compound with pH-Dependent Solubility.
Chung J, Alvarez-Nunez F, Chow V, Daurio D, Davis J, Dodds M, Emery M, Litwiler K, Paccaly A, Peng J, Rock B, Wienkers L, Yang C, Yu Z, Wahlstrom J. (2015) J. Pharm. Sci. Jan. 15
The potency–insolubility conundrum in pharmaceuticals: Mechanism and solution for hepatitis C protease inhibitors.

Connelly PR, Snyder PW, Zhang Y, McClain B, Quinn BP, Johnston S, Medek A, Tanoury J, Griffith J, Walters WP, Dokou E, Knezic D, Bransford P. (2015) Biophysical Chem. 196:100-108

Physiologically based pharmacokinetic modelling in drug discovery and development: A pharmaceutical industry perspective.

Jones HM, Chen Y, Gibson C, Heimbach T, Parrott N, Peters SA, Snoeys J, Upreti VV, Zheng M, Hall SD. (2014) Clin. Pharmacol. Ther. 10.1002/cpt.37
Predicting drug-drug interactions involving multiple mechanisms using physiologically based pharmacokinetic modeling: A case study with ruxolitinib.
Shi JG, Fraczkiewicz G, Williams W, Yeleswaram S. (2014) Clin. Pharmacol. Ther. 10.1002/cpt.30
Novel Orally Swallowable IntelliCap(®) Device to Quantify Regional Drug Absorption in Human GI Tract Using Diltiazem as Model Drug.
Becker D, Zhang J, Heimbach T, Penland RC, Wanke C, Shimizu J, Kulmatycki K. (2014) AAPS PharmSciTech. Dec;15(6):1490-7.
Dissolution testing combined with computer simulation technology to evaluate the bioequivalence of domestic amoxicillin capsule.
Pan RX, Gao Y, Chen WL, Li YL, Hu CQ. (2014) Yao Xue Xue Bao. Aug;49(8):1155-61.
Model-Based Bioequivalence assessment of a commercial Azithromycin Capsule against Pfizer Zithromax® Tablet marketed in Jamaica
Adebayo AS, McFarlane N (2014) J. Appl. PharmSci. 4(10) 62-68
Biopharmaceutical profiling of new antitumor pyrazole derivatives.
Anuta V, Nitulescu GM, Dinu-Pîrvu CE, Olaru OT. (2014) Molecules. Oct 13;19(10):16381-401
The potency-insolubility conundrum in pharmaceuticals: Mechanism and solution for hepatitis C protease inhibitors.
Connelly PR, Snyder PW, Zhang Y, McClain B, Quinn BP, Johnston S, Medek A, Tanoury J, Griffith J, Walters WP, Dokou E, Knezic D, Bransford P. (2014) Biophysical Chem. Sept. 18
Evaluation of a Three Compartment In Vitro Gastrointestinal Simulator Dissolution Apparatus to Predict In Vivo Dissolution.
Takeuchi S, Tsume Y, Amidon GE, Amidon GL. (2014) J Pharm Sci. Sept 22.
Elucidation of Arctigenin Pharmacokinetics After Intravenous and Oral Administrations in Rats: Integration of In Vitro and In Vivo Findings via Semi-mechanistic Pharmacokinetic Modeling.
Gao Q, Zhang Y, Wo S, Zuo Z. (2014) AAPS J. Oct. 2
Preparation and Evaluation of High Dispersion Stable Nanocrystal Formulation of Poorly Water-Soluble Compounds by Using Povacoat.
Yuminoki K, Seko F, Horii S, Takeuchi H, Teramoto K, Nakada Y, Hashimoto N. (2014) J Pharm Sci. Sep 10.
Application of Absorption Modeling to Predict Bioequivalence Outcome of Two Batches of Etoricoxib Tablets.
Mitra A, Kesisoglou F, Dogterom P. (2014) AAPS PharmSciTech. Sep 3.
Development of nanocrystal formulation of meloxicam with improved dissolution and pharmacokinetic behaviors.
Ochi M, Kawachi T, Toita E, Hashimoto I, Yuminoki K, Onoue S, Hashimoto N. (2014) Int J Pharm. Aug 17;474(1-2):151-156.
Intestinal transport of TRH analogs through PepT1: the role of in silico and in vitro modeling.
Bagul P, Khomane KS, Kesharwani SS, Pragyan P, Nandekar PP, Meena CL, Bansal AK, Jain R, Tikoo K, Sangamwar AT. (2014) J Mol. Recognit. 27:609-617
Improvement of trospium-specific absorption models for fasted and fed states in humans.
Cvijic S, Langguth P. (2014) Biopharm Drug Dispos. Jul 17

PEGylated cyclodextrins as novel siRNA nanosystems: Correlations between polyethylene glycol length and nanoparticle stability.

Godinho BM, Ogier JR, Quinlan A, Darcy R, Griffin BT, Cryan JF, Caitriona MO. (2014) Int J Pharm. 473(1-2):105-112
Physiologically Based Absorption Modelling to Predict the Impact of Drug Properties on Pharmacokinetics of Bitopertin.
Parrott N, Hainzl D, Scheubel E, Krimmer S, Boetsch C, Guerini E, Martin-Facklam M. (2014) AAPS J. Jun. 27
Enhanced Solubility and Oral Bioavailability of y-Tocotrienol Using a Self-Emulsifying Drug Delivery System (SEDDS).
Alqahtani S, Alayoubi A, Nazzal S, Sylvester PW, Kaddoumi A. (2014) Lipids Jun 17.
Simulation of the In Vivo Exposure to Ibuprofen Based on In Vitro Dissolution Profiles from Solid Dosage Forms.
Popa DE, Lupuliasa D, Stanescu AA, Barca M, Burcea Dragomiroiu GTA, Miron DS, Radulescu FS. (2014) Farmacia 62(3):483
In vitro – in silico – in vivo drug absorption model development based on mechanistic gastrointestinal simulation and artificial neural networks: Nifedipine osmotic release tablets case study
Ilic M, Duriš J, Kovacevic I, Ibric S, Parojcic J. (2014) Eur J Pharm Sci. Jun 6.
Translational PK/PD modeling for cardiovascular safety assessment of drug candidates: Methods and examples in drug development.
Caruso A, Frances N, Meille C, Greiter-Wilke A, Hillebrecht A, Lave T. (2014) J Pharmacol Toxicol Methods. May 28
Pharmacokinetics of Paracetamol in Göttingen Minipigs: In Vivo Studies and Modeling to Elucidate Physiological Determinants of Absorption.
Suenderhauf C, Tuffin G, Lorentsen H, Grimm HP, Flament C, Parrott N. (2014) Pharm Res. May 3.
Testicular distribution and toxicity of a novel LTA4H inhibitor in rats.
Ward PD, La D. (2014) Toxicol Appl Pharmacol. Apr 22;278(1):26-30
Modelling the Absorption of Metformin with Patients Post Gastric Bypass Surgery.
Almukainzi M, Lukacova V, Löbenberg R. (2014) J Diabetes Metab 5:353

From Bench to Humans: Formulation Development of a Poorly Water Soluble Drug to Mitigate Food Effect.
Pandey P, Hamey R, Bindra DS, Huang Z, Mathias N, Eley T, Crison J, Yan B, Perrone R, Vemavarapu C. (2014) AAPS PharmSciTech. Jan 18.
Application of Physiologically Based Absorption Modeling to Formulation Development of a Low Solubility, Low Permeability Weak Base: Mechanistic Investigation of Food Effect.
Zhang H, Xia B, Sheng J, Heimbach T, Lin TH, He H, Wang Y, Novick S, Comfort A. (2014) AAPS PharmSciTech. Jan 17.
A Case Study of In Silico Modelling of Ciprofloxacin Hydrochloride/Metallic Compound Interactions.
Stojkovic A, Parojcic J, Djuric Z, Corrigan OI. (2013) AAPS PharmSciTech. Dec 5.
The Biopharmaceutics Classification System: Subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC.
Tsume Y, Mudie DM, Langguth P, Amidon GE, Amidon GL. (2014) Eur J Pharm Sci. Jan 28.
Physiologically based pharmacokinetic modeling of CYP3A4 induction by rifampicin in human: influence of time between substrate and inducer administration.
Baneyx G, Parrott N, Meille C, Iliadis A, Lavé T. (2014) Eur J Pharm Sci. Feb 12.

Clinical Pharmacokinetics of Buffered Propranolol Sublingual Tablet (Promptol™)—Application of a New “Physiologically Based” Model to Assess Absorption and Disposition.
Wang Y, Wang Z, Zuo Z, Tomlinson B, Lee BT, Bolger MB, Chow MS. (2013) AAPS J. Apr 19
Physiologically Based Pharmacokinetic Modelling to Predict Single- and Multiple-Dose Human Pharmacokinetics of Bitopertin
Parrott N, Hainzl D, Alberati D, Hofmann C, Robson R, Boutouyrie B, Martin-Facklam M. (2013) Clin Pharmacokinet. Apr 17
In Vitro Characterization of Axitinib Interactions with Human Efflux and Hepatic Uptake Transporters. Implications for Disposition and Drug Interactions.
Reyner E, Sevidal S, West MA, Clouser-Roche A, Freiwald S, Fenner K, Ullah M, Lee C, Smith BJ. (2013) Drug Metab Dispos. May 31
Compartmental absorption modeling and site of absorption studies to determine feasibility of an extended-release formulation of an HIV-1 attachment inhibitor phosphate ester prodrug.
Brown J, Chien C, Timmins P, Dennis A, Doll W, Sandefer E, Page R, Nettles RE, Zhu L, Grasela D. (2013) J Pharm Sci. 102(6):1742-51
Amorphous solid dispersions and nano-crystal technologies for poorly water-soluble drug delivery.
Brough C, Williams RO 3rd. (2013) Int J Pharm. Jun 7
Profiling Biopharmaceutical Deciding Properties of Absorption of Lansoprazole Enteric-Coated Tablets Using Gastrointestinal Simulation Technology.
Wu C, Sun L, Sun J, Yang Y, Ren C, Ai X, Lian H, He Z. (2013) Int J Pharm. Jun 24
Physiologically based pharmacokinetic and pharmacodynamic modeling of an antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in a mouse xenograft model of human breast cancer.
Zhang T, Li Y, Zou P, Yu JY, McEachern D, Wang S, Sun D. (2013) Biopharm. & Drug Dispos. DOI: 10.1002/bdd.1850
A Simplified PBPK Modeling Approach for Prediction of Pharmacokinetics of Four Primarily Renally Excreted and CYP3A Metabolized Compounds During Pregnancy.
Xia B, Heimbach T, Gollen R, Nanavati C, He H. (2013) AAPS J. Jul 9
In Vitro-In Vivo Correlation of Efavirenz Tablets Using GastroPlus®
Honório TD, Pinto EC, Rocha HV, Esteves VS, Dos Santos TC, Castro HC, Rodrigues CR, de Sousa VP, Cabral LM. (2013) AAPS PharmSciTech Aug. 14
Incorporation of Physiologically Based Pharmacokinetic Modeling in the Evaluation of Solubility Requirements for the Salt Selection Process: A Case Study Using Phenytoin.
Chiang PC, Wong H. (2013) AAPS J. Aug. 14
Utility of Physiologically Based Modeling and Preclinical In Vitro/In Vivo Data to Mitigate Positive Food Effect in a BCS Class 2 Compound.
Xia B, Heimbach T, Lin TH, Li S, Zhang H, Sheng J, He H. (2013) AAPS PharmSciTech Aug. 17
Use of Preclinical Dog Studies and Absorption Modeling to Facilitate Late Stage Formulation Bridging for a BCS II Drug Candidate.
Kesisoglou F. (2013) AAPS PharmSciTech. Sep 11.
Assessing the Risk of pH-Dependent Absorption for New Molecular Entities: A Novel in Vitro Dissolution Test, Physicochemical Analysis, and Risk Assessment Strategy.
Mathias NR, Xu Y, Patel D, Grass M, Caldwell B, Jager C, Mullin J, Hansen L, Crison J, Saari A, Gesenberg C, Morrison J, Vig BS, Raghavan K. (2013) Mol Pharm. Sep 13.
Investigation of clinical pharmacokinetic variability of an opioid antagonist through physiologically based absorption modeling.
Ding X, He M, Kulkarni R, Patel N, Zhang X. (2013) J Pharm Sci. 102(8):2859-74
PBPK models for the prediction of in vivo performance of oral dosage forms.
Kostewicz ES, Aarons L, Bergstrand M, Bolger MB, Galetin A, Hatley O, Jamei M, Lloyd R, Pepin X, Rostami A, Sjögren E, Tannergren C, Turner DB, Wagner C, Weitschies W, Dressman J. (2013) Eur J Pharm Sci. Sep 21
Effects of novel cathepsin K inhibitor ONO-5334 on bone resorption markers: a study of four sustained release formulations with different pharmacokinetic patterns.
Tanaka M, Hashimoto Y, Sekiya N, Honda N, Deacon S, Yamamoto M. (2013) J Bone Miner Metab. Oct 11
Biowaiver approach for biopharmaceutics classification system class 3 compound metformin hydrochloride using in silico modeling.
Crison JR, Timmins P, Keung A, Upreti VV, Boulton DW, Scheer BJ. (2012) J. Pharm. Sci. Feb. 14
In Silico Modeling for the Nonlinear Absorption Kinetics of UK-343,664: A P-gp and CYP3A4 Substrate.
Abuasal BS, Bolger MB, Walker DK, Kaddoumi A. (2012) Mol. Pharm. Feb. 2
Novel physiologically based pharmacokinetic modeling of patupilone for human pharmacokinetic predictions.
Xia B, Heimbach T, Lin T, He H, Wang Y, Tan E. (2012) Cancer Chemotherapy and Pharmacology 69(4)
The Use of Modeling Tools to Drive Efficient Oral Product Design.
Mathias NR, Crison J. (2012) AAPS J. May 30
Developability assessment of clinical drug products with maximum absorbable doses.
Ding X, Rose JP, Van Gelder J. (2012) Int. J. Pharm. 427(2):260-9
Parameters for pyrethroid insecticide QSAR and PBPK/PD models for human risk assessment.
Knaak JB, Dary CC, Zhang X, Gerlach RW, Tornero-Velez R, Chang DT, Goldsmith R, Blancato JN. (2012) Rev. Environ. Contam. Toxicol. 219:1-114
Preclinical Assessment of the Absorption and Disposition of the Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor GDC-0980 and Prediction of Its Pharmacokinetics and Efficacy in Human.
Salphati L, Pang J, Plise EG, Lee LB, Olivero AG, Prior WW, Sampath D, Wong S, Zhang X. (2012) Drug Metab. Dispos. 40(9):1785-96
Application of PBPK modeling to predict human intestinal metabolism of CYP3A substrates – An evaluation and case study using GastroPlus™
Heikkinen AT, Baneyx G, Caruso A, Parrott N. (2012) Eur. J. Pharm. Sci. 47(2):375-86
Developing In Vitro–In Vivo Correlation of Risperidone Immediate Release Tablet.
Saibi Y, Sato H, and Tachiki H. (2012) AAPS PharmSciTech June 14
Comparison of in vitro–in vivo release of Risperdal® Consta® microspheres
Rawata A, Bhardwajb U, Burgess DJ. (2012) Int. J. Pharm. 434(1):115-21
Selection of oral bioavailability enhancing formulations during drug discovery.
Zheng W, Jain A, Papoutsakis D, Dannenfelser RM, Panicucci R, Garad S. (2012) Drug Devel. Indus. Pharm. 38(2):235-47
In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.
Tsume Y, Langguth P, Garcia-Arieta A, Amidon GL. (2012) Biopharm. Drug Dispos. doi: 10.1002/bdd.1800
Circadian Variations in Exsorptive Transport: In Situ Intestinal Perfusion Data and In Vivo Relevance.
Okyar A, Dressler C, Hanafy A, Baktir G, Lemmer B, Spahn-Langguth H. (2012) Chronobiology International 29(4):443-453
Use of In Vitro-In Vivo Correlation to Predict the Pharmacokinetics of Several Products Containing a BCS Class 1 Drug in Extended Release Matrices.
Mirza T, Bykadi SA, Ellison CD, Yang Y, Davit BM, Khan MA. (2012) Pharm. Res. Aug. 22
Predicting feasibility and characterizing performance of extended-release formulations using physiologically based pharmacokinetic modeling.
Brown J, Crison J, Timmins P. (2012) Therapeutic Del. 3(9):1047-59
Pharmacokinetics and Pharmacodynamics of Phase II Drug Metabolizing/Antioxidant Enzymes Gene Response by Anti-cancer Agent Sulforaphane in Rat Lymphocytes
Wang H, Khor TO, Yang Q, Huang Y, Wu TY, Saw CL, Lin W, Androulakis IP, Kong AN. (2012) Mol. Pharm. Aug. 29
Modeling and simulation of the effect of proton pump inhibitors on magnesium homeostasis: part I. oral absorption of magnesium.
Bai JP, Hausman E, Lionberger R, Zhang X. (2012) Mol. Pharm. Oct. 11
Simulation of the pharmacokinetics of bisoprolol in healthy adults and patients with impaired renal function using whole-body physiologically based pharmacokinetic modeling.
Li GF, Wang K, Chen R, Zhao HR, Yang J, Zheng QS. (2012) Acta Pharmacol Sin. Oct. 22
Nilotinib preclinical pharmacokinetics and practical application toward clinical projections of oral absorption and systemic availability.
Xia B, Heimbach T, He H, Lin TH. (2012) Biopharm Drug Dispos. Oct. 24
Case Studies for Practical Food Effect Assessments across BCS/BDDCS Class Compounds using In Silico, In Vitro, and Preclinical In Vivo Data.
Heimbach T, Xia B, Lin TH, He H. (2012) AAPS J. Nov 10
Single-Dose Safety, Tolerability, and Pharmacokinetics of the Antibiotic GSK1322322, a Novel Peptide Deformylase Inhibitor.
Naderera OJ, Dumont E, Zhuc J, Kurtinecz M, Jones LS. (2013) Antimicrob Agents Chemother. Feb 12
Predicting Pharmacokinetic Profiles Using In Silico Derived Parameters.
Hosea NA, Jones HM. (2013) Mol Pharm. Feb 21
In vitro to in vivo extrapolation and physiologically based modeling of cytochrome P450 mediated metabolism in beagle dog gut wall and liver.
Heikkinen AT, Fowler S, Gray L, Li J, Peng Y, Yadava P, Railkar A, Parrott N. (2013) Mol Pharm. Feb. 25
Application of Target-Mediated Drug Disposition Model to Small Molecule Heat Shock Protein 90 Inhibitors.
Yamazaki S, Shen Z, Jiang Y, Smith BJ, Vicini P. (2013) Drug Metab Dispos. Apr 4
Pharmacokinetics of dietary cancer chemopreventive compound dibenzoylmethane in rats and the impact of nanoemulsion and genetic knockout of Nrf2 on its disposition
Lin, W, Hong JL, Shen G, Wu RT, Wang Y, Huang MT, Newmark HL, Huang Q, Khor TO, Heimbach T, Kong AN. (2011) Biopharm. Drug Dispos. 32:65–75
Development of a physiologically based model for oseltamivir and simulation of pharmacokinetics in neonates and infants.
Parrott N, Davies B, Hoffmann G, Koerner A, Lave T, Prinssen E, Theogaraj E, Singer T. (2011) Clin. Pharmacokinet. 50(9):613-23
The biowaivers extension for BCS Class III drugs: the effect of dissolution rate on on the bioequivalence of BCS Class III IR drugs predicted by computer simulation.
Tsume Y, Amidon GL. (2010) Mol Pharm. 7(4):1235-43
Dissolution modeling of bead formulations and predictions of bioequivalence for a highly soluble, highly permeable drug.
Sperry DC, Thomas SJ, Lobo E. (2010) Mol Pharm. Aug 12.
A pH-Dilution Method for Estimation of Biorelevant Drug Solubility along the Gastrointestinal Tract: Application to Physiologically Based Pharmacokinetic Modeling.
Gao Y, Carr RA, Spence JK, Wang WW, Turner TM, Lipari JM, Miller JM. (2010) Mol Pharm. 7(5):1516-26
In Vitro-In Vivo Correlation for Gliclazide Immediate-Release Tablets Based on Mechanistic Absorption Simulation.
Grbic S, Parojcic J, Ibric S, Djuric Z. (2010) AAPS PharmSciTech. Dec 23
Black tea improves attention and self-reported alertness.
De Bruin EA, Rowson MJ, Van Buren L, Rycroft JA, Owen GN. (2010) Appetite. Dec 21.
Prediction of Oral Pharmacokinetics of cMet Kinase Inhibitors in Humans: Physiologically Based Pharmacokinetic Model versus Traditional One Compartment Model.
Yamazaki S, Skaptason J, Romero D, Vekich S, Jones HM, Tan W, Wilner KD, Koudriakova T. (2010) Drug Metab. Dispos. Nov 23
Utility of Physiologically Based Absorption Modeling in Implementing Quality by Design in Drug Development.
Zhang X, Lionberger RA, Davit BM, Yu LX. (2011) AAPS J. 13(1):59-71
The Application of Physiologically Based Pharmacokinetic Modelling to Understanding the Clinical Pharmacokinetics of UK-369,003.
Watson KJ, Davis J, Jones HM. (2011) Drug Metab Dispos. Mar 30
Simulation of human intravenous and oral pharmacokinetics of 21 diverse compounds using physiologically based pharmacokinetic modelling.
Jones HM, Gardner IB, Collard WT, Stanley PJ, Oxley P, Hosea NA, Plowchalk D, Gernhardt S, Lin J, Dickins M, Rahavendran SR, Jones BC, Watson KJ, Pertinez H, Kumar V, Cole S. (2011) Clin Pharmacokinet. 1;50(5):331-47
Effect of gastric pH on the pharmacokinetics of a BCS Class II compound in dogs: Utilization of an artificial stomach and duodenum dissolution model and GastroPlus™ simulations to predict absorption.
Bhattachar SN, Perkins EJ, Tan JS, Burns LJ. (2011) J Pharm Sci. Jun 16.
Physiological modeling and assessments of regional drug bioavailability of danoprevir to determine whether a controlled release formulation is feasible.
Reddy MB, Connor A, Brennan BJ, Morcos PN, Zhou A, McLawhon P, Fretland A, Evans P, Smith P, Tran JQ. (2011) Biopharm Drug Dispos. June 9.
Pre-clinical and clinical pharmacokinetics of PF-02413873, a non-steroidal progesterone receptor antagonist.
Bungay PJ, Tweedy S, Howe DC, Gibson KR, Jones HM, Mount NM. (2011) Drug Metab Dispos. May 4
Application of PBPK modelling in drug discovery and development at Pfizer.
Jones HM, Dickins M, Youdim K, Gosset JR, Attkins NJ, Hay TL, Gurrell IK, Logan YR, Bungay PJ, Jones BC, Gardner IB. (2011) Xenobiotica 0(0):1-13
The role of predictive biopharmaceutical modeling and simulation in drug development and regulatory evaluation.
Jiang W, Kim S, Zhang X, Lionberger RA, Davit BM, Conner DP, Yu LX. (2011) Int J Pharm. 418(2):151-60

 

 

 

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