Association between pharmacokinetics of lenvatinib in healthy subjects and genetic polymorphisms of ABCB1 3435C>T and ABCB1 2677G>T/A. (2nd December 2021)

• Record Type: Journal Article
• Authors: Song, Haojing; Bai, Wanjun; Sun, Xue; Qiu, Bo; Guo, Nini; Guo, Caihui; Hu, Yiting; Dong, Zhanjun
• Is Part Of: Xenobiotica. Volume 51:Number 12(2021)
• Page Start: 1463
• Page End: 1469
• Publication Date: 2021-12-02
• Subjects: Lenvatinib -- genetic polymorphisms -- pharmacokinetics -- ABC transporter; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.1080/00498254.2021.2023913
• Languages: English
• ISSNs: 0049-8254

Abstract

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.