Physiologically-Based Pharmacokinetic Modeling Approach to Predict Rifampin-Mediated Intestinal P-Glycoprotein Induction.

ABSTRACT: Physiologically-based pharmacokinetic (PBPK) modeling is a powerful tool to quantitatively describe drug disposition profiles in vivo, thereby providing an alternative to predict drug-drug interactions (DDIs) that have not been tested clinically. This study aimed to predict effects of rifampin-mediated intestinal P-glycoprotein (Pgp) induction on pharmacokinetics of Pgp substrates via PBPK modeling. First, we selected four Pgp substrates (digoxin, talinolol, quinidine, and dabigatran etexilate) to derive in vitro to in vivo scaling factors for intestinal Pgp kinetics. Assuming unbound Michaelis-Menten constant (K_m ) to be intrinsic, we focused on the scaling factors for maximal efflux rate (J_max ) to adequately recover clinically observed results. Next, we predicted r

SUBMITTER: Yamazaki S 

PROVIDER: S-EPMC6765699 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature