在中国健康人群中，多态性与格列齐特口服清除率受损有关。
Polymorphism Is Associated with Impaired Oral Clearance of Gliclazide in Healthy Chinese.
作者信息
Chow Elaine, Poon Emily Wm, Fok Benny Sp, Chan Juliana Cn, Tomlinson Brian
机构信息
Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Hong Kong.
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
出版信息
Pharmgenomics Pers Med. 2019 Dec 31;12:397-401. doi: 10.2147/PGPM.S226200. eCollection 2019.
BACKGROUND
Previous studies suggest gliclazide is metabolised primarily by CYP2C19 rather than CYP2C9, unlike other sulphonylureas. and 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 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).
CONCLUSION
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.
背景
先前的研究表明，与其他磺脲类药物不同，格列齐特主要通过CYP2C19而非CYP2C9代谢，且CYP2C19基因多态性在亚洲人中更为常见。
方法
我们对15名健康中国男性受试者单次口服80mg格列齐特后，研究了CYP2C19基因多态性对其药代动力学的影响。
结果
在慢代谢者（CYP2C19 2/2，n = 4）中，血浆曲线下面积比中代谢者（CYP2C19 1/2杂合子，n = 7）和快代谢者（CYP2C19 1/1，n = 4）高近两倍（p<0.001）。慢、中、快代谢者的表观口服清除率分别为平均（标准差）0.70（0.12）、1.22（0.22）和1.52（0.47）mL/min/kg（p = 0.005）。
结论
CYP2C19基因多态性与格列齐特总浓度升高和口服清除率降低有关。有必要进行药物遗传学研究，以探讨CYP2C19基因多态性对治疗反应和低血糖的影响。
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