CYP2C19*2 Polymorphism Is Associated with Impaired Oral Clearance of Gliclazide in Healthy Chinese

Elaine Chow; Emily Wm Poon; Benny Sp Fok; Juliana Cn Chan; Brian Tomlinson

doi:10.2147/PGPM.S226200

CYP2C192* Polymorphism Is Associated with Impaired Oral Clearance of Gliclazide in Healthy Chinese

Pharmgenomics Pers Med. 2019 Dec 31:12:397-401. doi: 10.2147/PGPM.S226200. eCollection 2019.

Authors

Elaine Chow^{1

2}, Emily Wm Poon², Benny Sp Fok¹, Juliana Cn Chan², Brian Tomlinson^{1

2

3}

Affiliations

¹ Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Hong Kong.
² Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
³ Faculty of Medicine, Macau University of Science & Technology, Taipa, Macau.

Abstract

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: CYP2C19; gliclazide; pharmacogenetics.