Drug design, development and therapy
Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions of Aficamten in the Chinese Population
By Wang Z, Wu X, Jia R and 1 others.
Abstract
Background
Aficamten is a next-generation cardiac myosin inhibitor (CMI) developed for the treatment of obstructive hypertrophic cardiomyopathy (oHCM). Although extensive clinical pharmacology studies have been conducted in Caucasian populations, limited information is available regarding drug-drug interaction (DDI) risks in the Chinese population. Given the contribution of multiple cytochrome P450 (CYP) enzymes to aficamten metabolism and inter-ethnic differences in CYP-mediated metabolic capacity, it is important to characterize DDI risks and associated changes in aficamten exposure in Chinese subjects.
Methods
A whole-body physiologically-based pharmacokinetic (PBPK) model of aficamten was developed using clinical data from Caucasian subjects and extrapolated to the Chinese population. The PBPK model was subsequently applied to compare aficamten exposure between Chinese and Caucasian populations and to predict DDIs in Chinese subjects.