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 in | Pharmacogenomics and personalized medicine Vol. 12; pp. 397 - 401 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New Zealand
Taylor & Francis Ltd
01.01.2019
Dove |
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| Abstract | 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. |
|---|---|
| AbstractList | BackgroundPrevious studies suggest gliclazide is metabolised primarily by CYP2C19 rather than CYP2C9, unlike other sulphonylureas. CYP2C19 *2 and *3 polymorphisms are more common in Asians. MethodsWe investigated the effect of CYP2C19 polymorphisms on gliclazide pharmacokinetics in 15 healthy male Chinese subjects after a single 80mg oral dose. ResultsIn 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). ConclusionCYP2C19*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. 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. 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. |
| Author | Chow, Elaine Tomlinson, Brian Fok, Benny Sp Chan, Juliana Cn Poon, Emily Wm |
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| Keywords | CYP2C19 pharmacogenetics gliclazide |
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| Snippet | Previous studies suggest gliclazide is metabolised primarily by CYP2C19 rather than CYP2C9, unlike other sulphonylureas.
and
polymorphisms are more common in... Background: Previous studies suggest gliclazide is metabolised primarily by CYP2C19 rather than CYP2C9, unlike other sulphonylureas. CYP2C19 *2 and *3... BackgroundPrevious studies suggest gliclazide is metabolised primarily by CYP2C19 rather than CYP2C9, unlike other sulphonylureas. CYP2C19 *2 and *3... |
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| SubjectTerms | Chromatography Diabetes Drug dosages Genotype & phenotype Heterozygotes Hypoglycemia Metabolism Metabolites Original Research Pharmacokinetics |
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| Title | CYP2C192 Polymorphism Is Associated with Impaired Oral Clearance of Gliclazide in Healthy Chinese |
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