Influences of ABC transporter and CYP3A4/5 genetic polymorphisms on the pharmacokinetics of lenvatinib in Chinese healthy subjects.
Purpose: To investigate whether the CYP3A4/5 and ABC transporter genetic polymorphisms could affect the pharmacokinetics of lenvatinib in Chinese healthy subjects. Methods: Thirty-two healthy Chinese volunteers were enrolled and took oral administration of 8 mg lenvatinib. Plasma concentration of le...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 76; no. 8; pp. 1125 - 1134 |
|---|---|
| Autores principales: | , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Aug2020
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=144499039&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 144499039 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Aug2020 vid: 76 iid: 8 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 144499039 143996420 144499039 144499039 10.1007/s00228-020-02879-z 144499039 ppf: 1125 ppct: 9 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Influences of ABC transporter and CYP3A4/5 genetic polymorphisms on the pharmacokinetics of lenvatinib in Chinese healthy subjects. aug: au: Li, Jiaming Wang, Xiaoqian Ning, Chen Wang, Zhaoyu Wang, Yao Zheng, Ming Zhang, Siliang Lu, Yang Zhang, Yongjie Li, Ning Chen, Xijing Zhao, Di affil: Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, #639 Longmian Avenue, Jiangning District, 211198, Nanjing, China sug: subj: Protein Kinase Inhibitors Pharmacokinetics Antineoplastic Agents Pharmacokinetics Polymorphism, Genetic ATP Binding Cassette Transporters Human China Antineoplastic Agents Administration and Dosage Antineoplastic Agents Blood Gas Chromatography-Mass Spectrometry Genotype Heterozygote Alleles ab: Purpose: To investigate whether the CYP3A4/5 and ABC transporter genetic polymorphisms could affect the pharmacokinetics of lenvatinib in Chinese healthy subjects. Methods: Thirty-two healthy Chinese volunteers were enrolled and took oral administration of 8 mg lenvatinib. Plasma concentration of lenvatinib was determined by UPLC-MS/MS, the CYP3A4*1G, CYP3A5*3, ABCB1 (3435 C>T, 1236 C>T, 2677 G>T/A), ABCG2 (421 C>A, 34 G>A), and ABCC2-24 C>T genotypes were determined by SnapShot Technique. Results: In ABCB1 3435T carriers (n = 19), AUC0–120h (815.7 (701.9–923.9) ng·h/mL) and AUC0-∞ (843.3 (722.2–977.7) ng·h/mL) were significantly higher than ABCB1 3435CC homozygous subjects (n = 13, 575.3 (513.7–756.9) ng·h/mL and 590.0 (540.5–782.0) ng·h/mL, respectively); on the contrary, the clearance (CL/F) of ABCB1 3435T carriers was significantly lower (9.5 (8.2–11.1) L/h vs. 13.6 (10.4–14.8) L/h). And the Cmax in CYP3A4*1G/*1G allele carrier subjects was higher than *1 carrier (73.4 ng/mL vs. 53.5 (46.1–60.6) ng/mL), but did not reach the level of significantly statistical difference. Genetic polymorphisms of ABCC2, ABCG2, and CYP3A5 could not influence pharmacokinetic parameters of lenvatinib. Conclusions: This work presented an evidence that the ABCB1 3435 C>T polymorphism could significantly affect the exposure and clearance of lenvatinib. These findings may explain the reasons for the huge inter-individual differences in lenvatinib, and should contribute to clinical individualized treatment. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|