Cluster Gauss-Newton method analyses of PBPK model parameter combinations of coproporphyrin-I based on OATP1B-mediated rifampicin interaction studies.

ABSTRACT: Coproporphyrin I (CP-I) is an endogenous biomarker supporting the prediction of drug-drug interactions (DDIs) involving hepatic organic anion transporting polypeptide 1B (OATP1B). We previously constructed a physiologically-based pharmacokinetic (PBPK) model for CP-I using clinical DDI data with an OATP1B inhibitor, rifampicin (RIF). In this study, PBPK model parameters for CP-I were estimated using the cluster Gauss-Newton method (CGNM), an algorithm used to find multiple approximate solutions for nonlinear least-squares problems. Eight unknown parameters including the hepatic overall intrinsic clearance (CL_int,all ), the rate of biosynthesis (v_syn ), and the OATP1B inhibition constant of RIF(K_i,u,OATP ) were estimated by fitting to the observed CP-I blood

SUBMITTER: Yoshikado T 

PROVIDER: S-EPMC9574750 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature