Effects of the <i>ABCB1</i> and <i>ABCG2</i> polymorphisms on the pharmacokinetics of afatinib in healthy Chinese volunteers
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1. Afatinib is an oral, selective tyrosine kinase inhibitor (TKI) primarily transported by P-glycoprotein (MDR1, gene code <i>ABCB1</i>) and breast cancer resistance protein (BCRP, gene code <i>ABCG2</i>). In the present study, the effects of <i>ABCB1</i> and <i>ABCG2</i> genetic polymorphisms on the pharmacokinetics of afatinib in healthy Chinese were investigated. 2. Blood samples from 24 healthy participants who received afatinib were used for genotyping <i>ABCB1</i> (1236C>T, 2677G > T/A, 3435C>T) and <i>ABCG2</i> (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 <i>ABCB1</i> 1236CC–3435CC were remarkably higher than in other genotype subjects. No significant differences of afatinib exposure were found between the <i>ABCG2</i> wild-type and heterozygous groups. 4. The <i>ABCB1</i> genetic polymorphism influenced the plasma exposure of afatinib, and gene testing before drug administration may be useful for clinically individualized use of afatinib. Our data suggest the usefulness of afatinib pharmacogenetics in treatment optimization.
