https://orcid.org/0000-0002-4147-3387
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.
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Acknowledgements
We would like to thank the nurses and staff of the Division of Clinical Pharmacology, The Chinese University of Hong Kong for recruitment of participants and conduct of study. We would like to thank all study participants.
Ethical Statement
Written informed consent was obtained from all participants. The study has been approved by the Joint Clinical Research Ethics Committee of the Chinese University of Hong Kong and New Territories East Cluster before the start of the study. The study was conducted in accordance with International Council for Harmonisation (ICH) Good clinical practice. The study was registered at Clinical Trials.gov NCT02643329. This study has been presented at the International Diabetes Federation Congress, December 2017, Abu Dhabi.
Data Sharing Statement
The deidentified patient data generated during and/or analysed during the current study are available from the corresponding author on reasonable request 9 months after publication and up to 3 years post-publication.
Disclosure
The bioequivalence study was supported by Bright Future Pharmaceuticals Laboratories Limited, Hong Kong. The authors have no financial interest or conflict with the subject material discussed in this manuscript. No writing assistance was utilised in the production of this manuscript.