CYP2 C19遗传多态性对中国健康受试者西酞普兰代谢的影响

来源 :中国临床药理学杂志 | 被引量 : 0次 | 上传用户:qhl7901
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目的:研究中国健康男性受试者CYP2C19遗传多态性对西酞普兰体内代谢的影响。方法24名中国健康男性受试者空腹单次口服西酞普兰片20 mg,服药前采静脉血,乙二胺四乙酸( EDTA)抗凝,提取DNA,测定其基因型。分别在服药前和服药后一定时间点采静脉血各5 mL,离心取血浆,用HPLC-MS/MS法检测西酞普兰血药浓度,比较不同基因型受试者西酞普兰药代动力学的差异。结果2例受试者(8.33%)为CYP2C19慢代谢;10例为CYP2C19快代谢,其中纯合子12例(50%)、杂合子10例(41.67%)。西酞普兰的代谢受CYP2C19的基因多态性影响较大,但也可能受年龄和体重的影响。结论西酞普兰临床应用时应查明患者CYP2C19基因型,并参考其年龄、体重等情况给药。“,”Objective To investigate the effets of cytochrome CYP2C19 gene polymorphism on the pharmacokinetics of citalopram in Chinese healthy male volunteers.Methods Twenty-four Chinese healthy male volunteers were orally administered with a single dose of citalopram 20 mg.The venous blood samples were collected , using anticoagulantion EDTA to extract DNA, and the genotype was detected .The blood sam-ples(5 mL) from the bolunteers were collected before and after the ad-ministration of citalopram and plasma was taken .The plasma concentra-tion of citalopram was examined by HPLC -MS/MS method .The geno-type CYP2 C19 was measured by PCR -based sequencing.The measure-ments were performed by HPLC -MS/MS.Pharmacokinetic differences of citalopram on patients with different genotypes were compared .Results Two out of 24 volunteers were poor metabolizing genotype ( PM ) , and 22 were extensive metabolizers (EM).Among the EM 12 were homozy-gotes and 10 were heterozygotes.The pharmacokinetic of citalopram was largely influenced by CYP2 C19 genetic polymorphism , and also effected by the volunteers′age and weight.Conclusion The CYP2 C19 genotype of patients should be detected before the clinical appliaction of citalo-pram, and the age as well as weight also need to be considered .
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