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.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Correction Statement
This article has been republished with minor changes. These changes do not impact the academic content of the article.