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

Previous studies suggest gliclazide is metabolised primarily by CYP2C19 rather than CYP2C9, unlike other sulphonylureas. and polymorphisms are more common in Asians. We investigated the effect of CYP2C19 polymorphisms on gliclazide pharmacokinetics in 15 healthy male Chinese subjects after a single...

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Published inPharmacogenomics and personalized medicine Vol. 12; pp. 397 - 401
Main Authors Chow, Elaine, Poon, Emily Wm, Fok, Benny Sp, Chan, Juliana Cn, Tomlinson, Brian
Format Journal Article
LanguageEnglish
Published New Zealand Taylor & Francis Ltd 01.01.2019
Dove
Subjects
Chromatography
Diabetes
Drug dosages
Genotype & phenotype
Heterozygotes
Hypoglycemia
Metabolism
Metabolites
Original Research
Pharmacokinetics
CYP2C19
pharmacogenetics
gliclazide
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Summary:Previous studies suggest gliclazide is metabolised primarily by CYP2C19 rather than CYP2C9, unlike other sulphonylureas. and polymorphisms are more common in Asians. We investigated the effect of CYP2C19 polymorphisms on gliclazide pharmacokinetics in 15 healthy male Chinese subjects after a single 80mg oral dose. In poor metabolisers ( , n=4), plasma area-under-the-curve was higher by nearly two-fold compared with intermediate metabolisers ( and heterozygotes, n=7) and extensive metabolisers ( , 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). 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.
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ISSN:1178-7066
1178-7066
DOI:10.2147/PGPM.S226200