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

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 C-max (p < 0.01) and lambda z (p < 0.05), but higher t(1/2) (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 t(1/2) (p < 0.01), but lower lambda z (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 t(1/2) (p < 0.01) and lower lambda z (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.

Automated summary

This study aimed to evaluate the impact of genetic polymorphisms on the pharmacokinetics of lenvatinib in the Chinese population. The results showed that ABCB1 3435 C>T and ABCB1 2677 G>T/A polymorphisms were associated with the pharmacokinetic variability of lenvatinib in Chinese individuals.