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

Abstract

1. 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 were 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 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.

Keywords:

• Afatinib
• ABCB1
• ABCG2
• pharmacokinetics

Disclosure statement

The authors declare that they have no conflicts of interest.

Additional information

Funding

This study was supported by the fund: National New Drug Innovation Program of China (No. 2017ZX09301004), National Natural Science Foundation of China (Nos. 81473272 and No. 81373426), “Double First-Class" initiative Innovation team project of China Pharmaceutical University (No. CPU2018GY29), and the Fundamental Research Funds for the Central Universities (No. 2632018PT02).