Effects of the ABCB1 and ABCG2 polymorphisms on the pharmacokinetics of afatinib in healthy Chinese volunteers

Abstract1. Afatinib is an oral, selective tyrosine kinase inhibitor (TKI) primarily transported by P-glycoprotein (MDR1, gene code ABCB1) and breast cancer resistance protein (BCRP, gene code ABCG2). In the present study, the effects of ABCB1 and ABCG2 genetic polymorphisms on the pharmacokinetics of afatinib in healthy Chinese was investigated.2. Blood samples from 24 healthy participants who received afatinib were used for genotyping ABCB1 (1236C > T, 2677G > T/A, 3435C > T) and ABCG2 (34G > A, 421C > A) polymorphisms. Subsequently, the association between afatinib plasma concentrations and target single-nucleotide polymorphisms (SNPs) was analyzed.3. Among the five polymorphisms, plasma concentrations of afatinib in healthy subjects with ABCB1 1236CC-3435CC were remarkably higher than in other genotype subjects. No significant differences of afatinib exposure were found between the ABCG2 wild type and heterozygous groups.4. The ABCB1 genetic polymorphism influenced the plasma exposure of afatinib, and ...