Investigation of the Impact of CYP3A5 Polymorphism on Drug-Drug Interaction between Tacrolimus and Schisantherin A/Schisandrin A Based on Physiologically-Based Pharmacokinetic Modeling.

ABSTRACT: Wuzhi capsule (WZC) is commonly prescribed with tacrolimus in China to ease drug-induced hepatotoxicity. Two abundant active ingredients, schisantherin A (STA) and schisandrin A (SIA) are known to inhibit CYP3A enzymes and increase tacrolimus's exposure. Our previous study has quantitatively demonstrated the contribution of STA and SIA to tacrolimus pharmacokinetics based on physiologically-based pharmacokinetic (PBPK) modeling. In the current work, we performed reversible inhibition (RI) and time-dependent inhibition (TDI) assays with CYP3A5 genotyped human liver microsomes (HLMs), and further integrated the acquired parameters into the PBPK model to predict the drug-drug interaction (DDI) in patients with different CYP3A5 alleles. The results indicated STA was a time-depend

SUBMITTER: He Q 

PROVIDER: S-EPMC7997453 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature