Effect of the CYP2C19 genotype on the pharmacokinetics of icotinib in healthy male volunteers.

European Journal of Clinical Pharmacology
Can-Jun RuanPei Hu

Abstract

Icotinib hydrochloride {4-[(3-ethynylphenyl)amino]-6,7-benzo-12-crown-4-quinazoline hydrochloride}, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), was designed for the treatment of non-small cell lung cancer (NSCLC). In the present study, we investigated the influence of the CYP2C19*2 and CYP2C19*3 alleles on the pharmacokinetics of icotinib in healthy Chinese volunteers. In a single-dose pharmacokinetic study, 12 healthy Chinese volunteers received an oral dose of 600 mg of icotinib. Plasma was sampled for up to 72 h post-dose, followed by quantification of icotinib by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS-MS). Five subjects genotyped as homozygous extensive metabolizers (CYP2C19*1/*1), 6 subjects genotyped as heterozygous extensive metabolizers (CYP2C19*1/*2 or CYP2C19*1/*3), and 1 subject genotyped as a poor metabolizer (CYP2C19*2/*3) and was withdrawn from the research because of urticaria. The mean icotinib AUC(0-∞) and C(max) (14.56 ±5.31 h mg/L and 2.32 ± 0.49 μg/mL) in homozygous EMs was 1.56 and 1.41-fold lower than that in heterozygous EMs (22.7 ± 6.11 and 3.28 ± 0.48, P = 0.046 and 0.047). The mean CL/F (44.18 ± 12.17 L/h) in homozygous EMs was 1.55-fold hi...Continue Reading

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Citations

Nov 29, 2015·Cancer Chemotherapy and Pharmacology·K E BurnsN A Helsby
Nov 21, 2012·Drug Metabolism and Pharmacokinetics·Takeshi HirotaIchiro Ieiri
Dec 3, 2014·Drug Discovery Today·Yi-Long WuYumei Yang
May 9, 2015·European Journal of Clinical Pharmacology·M PawlowskaE Sieradzki
Jan 17, 2019·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Rashmi R Shah, Devron R Shah
Mar 5, 2014·Expert Opinion on Pharmacotherapy·Yong-Song GuanMei Li
Jul 28, 2021·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Chen SunJiang Zheng

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