Association between pharmacokinetics of lenvatinib in healthy subjects and genetic polymorphisms of ABCB1 3435C>T and ABCB1 2677G>T/A

Abstract

The aim of this study was to evaluate the impact of genetic polymorphisms in the pharmacokinetics of metabolism and transportation of lenvatinib in the Chinese population. Sixty-three healthy Chinese individuals were recruited and administered with a single dose of 4 mg lenvatinib. Allelic discriminations for 10 SNPs of CYP3A4 (20230 G>A(*1G)), CYP3A5 (6986 A>G(*3)), ABCB1 (1236 C>T, 2677 G>T/A, 3435 C>T), ABCG2 (421 C>A, 34 G>A), ABCC2 (-24 C>T, 1249 G>A, 3972 C>T) were performed. The concentrations of lenvatinib in the plasma were determined by UPLC-MS/MS. Under the fasting condition, individuals carrying of ABCB1 3435 C>T genotype presented lower Cmax (p < 0.01) and λz (p < 0.05), but higher t1/2 (p < 0.05) than those carrying C/C and T/T genotypes. For ABCB1 2677 G>T/A variant, individuals with the G/T and A/G genotype showed higher AUC (p < 0.05) and t1/2 (p < 0.01), but lower λz (p < 0.05) than those carrying G/G genotypes. Individuals with the A/T, A/A and T/T genotype had higher AUC, but no significant differences (p > 0.05) were observed. They also had higher t1/2 (p < 0.01) and lower λz (p < 0.01) than those carrying G/G genotypes. Under the fed condition, no difference in any pharmacokinetic parameters were observed with any polymorphisms in the 10 fragments. Data in this paper had demonstrated that polymorphisms ABCB1 3435 C>T and ABCB1 2677 G>T/A were associated with the pharmacokinetic variability of lenvatinib.