IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 4: Prediction accuracy and software comparisons with improved data and modelling strategies

Authors: Ahmad A, Pepin X, Aarons L, Wang Y, Darwich AS, Wood JM, Tannergren C, Karlsson E, Patterson C, Thörn H, Ruston L, Mattinson A, Carlert S, Berg S, Murphy D, Engman H, Laru J, Barker R, Flanagan T, Abrahamsson B, Budhdeo S, Franek F, Moir AJ, Hanisch G, Pathak SM, Turner DB, Jamei M, Brown J, Good D, Vaidhyanathan S, Jackson C, Nicolas O, Beilles S, Nguefack JF, Louit G, Henrion L, Ollier C, Boulu L, Xu C, Heimbach T, Xiojun R, Lin W, Nguyen-Trung AT, Zhang J, He H, Wu F, Bolger MB, Mullin JM, van Osdol W, Szeto KX, Korjamo T, Pappinen S, Tuunainen J, Zhu W, Xia B, Daublain P, Wong S, Manthena V, Modi S, Schafer KJ, Schmid K, Lloyd R, Patel A, Tistaert C, Bevernage J, Nguyen MA, Lindley D, Carr RA, Rostami-Hodjeganad A
Publication: Eur J Pharm Biopharm
Keywords: ACAT, gastroplus, mechanistic absorption, pbbm, PBPK modeling, physiologically based biopharmaceutics modeling
Software: GastroPlus®
Division: Simulations Plus

Abstract

Oral drug absorption is a complex process depending on many factors, including the physicochemical properties of the drug, formulation characteristics and their interplay with gastrointestinal physiology and biology. Physiological-based pharmacokinetic (PBPK) models integrate all available information on gastro-intestinal system with drug and formulation data to predict oral drug absorption. The latter together with in vitro–in vivo extrapolation and other preclinical data on drug disposition can be used to predict plasma concentration-time profiles in silico. Despite recent successes of PBPK in many areas of drug development, an improvement in their utility for evaluating oral absorption is much needed. Current status of predictive performance, within the confinement of commonly available in vitro data on drugs and formulations alongside systems information, were tested using 3 PBPK software packages (GI-Sim (ver.4.1), Simcyp® Simulator (ver.15.0.86.0), and GastroPlusTM (ver.9.0.00xx)). This was part of the Innovative Medicines Initiative (IMI) Oral Biopharmaceutics Tools (OrBiTo) project.

By Amais Ahmad, Xavier Pepin, Leon Aarons, Yuya Wang, Adam S. Darwichc, J. Matthew Wood, Christer Tannergren, Eva Karlsson, Claire Patterson, Helena Thörn, Linette Ruston, Alex Mattinson, Sara Carlert, Staffan Berg, Donal Murphy, Helena Engman, Johanna Laru, Ric Barker, Talia Flanagan, Bertil Abrahamsson, Shanoo Budhdeo, Frans Franek, Andrea Moir, Gunilla Hanisch, Shriram M.Pathakd, David Turner, Masoud Jamei, Jonathan Brown, David Good, Shruthi Vaidhyanathan, Claire Jackson, Olivier Nicolas, Stephane Beilles, Jean-Flaubert Nguefack, Guillaume Louitf, Louis Henrion, Celine Ollier, Laurent Boulu, Christine Xu, Tycho Heimbach, Ren Xiojun, Wen Ling, Anh-Thu, Nguyen-Trung, Jin Zhang, Handan Heg, Fan Wu, Michael B. Bolger, James M.Mullinh, Bill van Osdol, Ke Szeto, Timo Korjamo, Sari Pappinen, Johanna tuunainen, Wei Zhu,  Binfeng Xia, Pierre Daublain, Suet Wong, Varma Manthena, Sweta Modi, Kerstin Julia Schäfer, Kartrin Schmid, Richard Lloyd, Aarti Patel, Christophe Tistaert, Jan Bevernage, Mai Anh Nguyen, David Lindley, Robert Carr, AminRostami-Hodjegan