Influence of Food Effect and ABCB1 Genetic Polymorphism (rs4148738) on Dabigatran Pharmacokinetics: A Population Modeling Study in Chinese Adults

The influence of ABCB1 and CES1 genetic variants on dabigatran plasma exposure is still uncertain. This investigation aimed to quantitatively evaluate how these polymorphisms affect dabigatran ester concentrations in healthy Chinese participants using a population pharmacokinetic (PopPK) framework. A total of 1,926 PK samples obtained from 123 healthy volunteers who received 150 mg of oral dabigatran under either fasting or fed conditions were examined through a PopPK analysis. The data were best represented by a two-compartment model featuring first-order absorption.

Food intake and the ABCB1 rs4148738 variant emerged as significant covariates. Under post-meal dosing, lag time (ALAG) and clearance (CL) increased by 2.65% and 0.51%, respectively, while the absorption rate constant (KA) decreased by 0.24%. Furthermore, carriers of the CT genotype for ABCB1 (rs4148738) exhibited a 0.38% rise in central distribution volume (V2). Overall, the PopPK model reliably described dabigatran pharmacokinetics in healthy Chinese adults and confirmed that both dietary state and ABCB1 polymorphism meaningfully alter dabigatran absorption and circulating levels.