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

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Abstract

Purpose

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.

Methods

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).

Results

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metabolizers (CYP2C19*1/*2 or CYP2C19*1/*3), and 1 subject genotyped as a poor metabolizer (CYP2C19*2/*3) and was withdrawn from the research because of urticaria.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 AUC0-∞ and Cmax (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 higher than that in heterozygous EMs (28.42 ± 9.23 L/h, P = 0.013).

Conclusions

The data showed that the pharmacokinetics of icotinib differ significantly between homozygous EMs and heterozygous EMs in CYP2C19.

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Authors and Affiliations

  1. Clinical Pharmacology Research Center, Peking Union Medical College Hospital and Chinese Academy of Medical Sciences, 1 Shuai Fu Yuan, Dong Chen District, Beijing, 100730, China

    Can-Jun Ruan, Dong-Yang Liu, Ji Jiang & Pei Hu

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  1. Can-Jun Ruan
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  2. Dong-Yang Liu
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  3. Ji Jiang
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  4. Pei Hu
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Correspondence to Pei Hu.

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Ruan, CJ., Liu, DY., Jiang, J. et al. Effect of the CYP2C19 genotype on the pharmacokinetics of icotinib in healthy male volunteers. Eur J Clin Pharmacol 68, 1677–1680 (2012). https://doi.org/10.1007/s00228-012-1288-4

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  • DOI: https://doi.org/10.1007/s00228-012-1288-4

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