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

Abstract

Physiologically based pharmacokinetic (PBPK) modeling has been extensively used to study the factors of effect drug absorption, distribution, metabolize and extraction progress in human. In this study, Compound A(CPD A) is a BCS Class II drug, which has been extensive applied in clinical as lipid-lowering drug, administered orally after food, they displayed positive food effects in human, A PBPK model was built to mechanistic investigate the food effect of CPD A tablet in our study. By using gastroplus™ software, the PBPK models accurately predicted the results of food effects and predicted data were within 2-fold error of the observed results. The PBPK model mechanistic illuminated the changes of pharmacokinetic values for the positive food effects of the compound in human. Here in, the PBPK modeling which were combined with ACAT absorption models in it, successfully simulated the food effect in human of the drug. The simulation results were proved that PBPK model can be able to serve as a potential tool to predict the food effect on certain oral drugs.

Predicting Oral Drug Absorption: Mini Review on Physiologically-Based Pharmacokinetic Models

“…A second area of application in which oral PBPK models can serve as a useful tool is in the investigation of pH and food effects on oral bioavailability [ 44 , 45 , 46 ]. Of the two phenomena, pH effects are much easier to deal with using PBPK models.…”

Regulatory utility of physiologically based pharmacokinetic modeling for assessing food impact in bioequivalence studies: A workshop summary report

“…[11][12][13][14][15] Several studies have shown the application of oral PBPK models for assessing food impact. [16][17][18][19][20][21][22][23] In addition, some reports have also pointed out the prospects and challenges related to the use of PBPK for assessing the impact of food. 1,24 However, there still exists a knowledge gap regarding the appropriate development, validation, and use of PBPK modeling approaches for food effect assessment, specifically for regulatory submission purposes.…”

Physiologically Based Pharmacokinetic Models Can Be Used to Predict the Unique Nonlinear Absorption Profiles of Vismodegib

“…Unlike traditional empirical models, PBPK models are mechanistic in nature, as they integrate physiological processes with drug properties to incorporate biological interactions with drugs, such as dissolution and metabolic enzyme kinetics, and experimental conditions, such as dosing under a fasted or fed state. (Jones et al, 2012;Zhuang and Lu, 2016;Li et al, 2017;Lin and Wong, 2017). In a typical PBPK model, organs are represented as anatomical compartments which are connected by systemic circulation carrying drug.…”

“…(Chiang et al, 2013), 2(Davies and Morris, 1993) , 3(Wong et al, 2009), 4(Wong et al, 2010), 5(Kondo et al, 2003), 6 (Ikegami et al, 2003, 7(Kararli, 1995), 8(Willmann et al, 2007), 9(Chen et al, 2008) , 10 (Hall et al, 2012 (Mandikian et al, 2018),12 (Li et al, 2017),13 (Helander and Fändriks, 2014), 14(Jones et al, 2006),15 (Graham et al, 2012),16 (Rabot et al, 1997) This article has not been copyedited and formatted. The final version may differ from this version.…”