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

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.

SUBMITTER: Chow E 

PROVIDER: S-EPMC6997415 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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<i>CYP2C19*2</i> Polymorphism Is Associated with Impaired Oral Clearance of Gliclazide in Healthy Chinese.

Chow Elaine E   Poon Emily Wm EW   Fok Benny Sp BS   Chan Juliana Cn JC   Tomlinson Brian B  

Pharmacogenomics and personalized medicine 20191231

<h4>Background</h4>Previous studies suggest gliclazide is metabolised primarily by CYP2C19 rather than CYP2C9, unlike other sulphonylureas. <i>CYP2C19 *2</i> and <i>*3</i> polymorphisms are more common in Asians.<h4>Methods</h4>We investigated the effect of CYP2C19 polymorphisms on gliclazide pharmacokinetics in 15 healthy male Chinese subjects after a single 80mg oral dose.<h4>Results</h4>In <i>CYP2C19</i> poor metabolisers (<i>*2/*2</i>, n=4), plasma area-under-the-curve was higher by nearly t  ...[more]

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