Work

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

Year: 2020

Type: article

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: gliclazide, pharmacogenetics, CYP2C19

Source: Pharmacogenomics and Personalized Medicine

DOI: 10.2147/pgpm.s226200

Authors: Elaine Chow, Emily Poon, Benny Siu Pong Fok, Juliana CN Chan, Brian Tomlinson

Institutions: Chinese University of Hong Kong, Macau University of Science and Technology

Language: English

Topic: Pharmacogenetics and Drug Metabolism

Subfield: Pharmacology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,836