CYP2C19*2 Polymorphism Is Associated with Impaired Oral Clearance of Gliclazide in Healthy Chinese
Received 6 August 2019
Accepted for publication 28 November 2019
Published 3 January 2020 Volume 2019:12 Pages 397—401
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Martin Bluth
Elaine Chow,1,2 Emily WM Poon,2 Benny SP Fok,1 Juliana CN Chan,2 Brian Tomlinson1–3
1Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Hong Kong; 2Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; 3Faculty of Medicine, Macau University of Science & Technology, Taipa, Macau
Correspondence: Elaine Chow Email email@example.com
Background: Previous studies suggest gliclazide is metabolised primarily by CYP2C19 rather than CYP2C9, unlike other sulphonylureas. CYP2C19 *2 and *3 polymorphisms are more common in Asians.
Methods: We investigated the effect of CYP2C19 polymorphisms on gliclazide pharmacokinetics in 15 healthy male Chinese subjects after a single 80mg oral dose.
Results: In CYP2C19 poor metabolisers (*2/*2, n=4), plasma area-under-the-curve was higher by nearly two-fold compared with intermediate metabolisers (*2 and *3 heterozygotes, n=7) and extensive metabolisers (*1/*1, n=4) (p<0.001). Apparent oral clearance was mean (SD) 0.70 (0.12), 1.22 (0.22) and 1.52 (0.47) mL/min/kg in poor, intermediate and extensive metabolisers, respectively (p = 0.005).
Conclusion: CYP2C19*2 polymorphism is associated with increased total gliclazide concentration and reduced oral clearance. Pharmacogenetic studies are warranted on the impact of CYP2C19 polymorphisms on treatment response and hypoglycaemia.
Keywords: gliclazide, pharmacogenetics, CYP2C19
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]