张逸凡, 陈笑艳, 郭颖杰, 司大勇, 周慧, 钟大放. 细胞色素P450 CYP2C9*3对格列本脲和氯诺昔康中国人体药代动力学的影响J. 药学学报, 2005, 40(9): 796-799.
引用本文: 张逸凡, 陈笑艳, 郭颖杰, 司大勇, 周慧, 钟大放. 细胞色素P450 CYP2C9*3对格列本脲和氯诺昔康中国人体药代动力学的影响J. 药学学报, 2005, 40(9): 796-799.
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ZHANG Yi-fan, CHEN Xiao-yan, GUO Ying-jie, SI Da-yong, ZHOU Hui, ZHONG Da-fang. Impact of cytochrome P450 CYP2C9 variant allele CYP2C9*3 on the pharmacokinetics of glibenclamide and lornoxicam in Chinese subjectsJ. Acta Pharmaceutica Sinica, 2005, 40(9): 796-799.
Citation: ZHANG Yi-fan, CHEN Xiao-yan, GUO Ying-jie, SI Da-yong, ZHOU Hui, ZHONG Da-fang. Impact of cytochrome P450 CYP2C9 variant allele CYP2C9*3 on the pharmacokinetics of glibenclamide and lornoxicam in Chinese subjectsJ. Acta Pharmaceutica Sinica, 2005, 40(9): 796-799.
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细胞色素P450 CYP2C9*3对格列本脲和氯诺昔康中国人体药代动力学的影响

Impact of cytochrome P450 CYP2C9 variant allele CYP2C9*3 on the pharmacokinetics of glibenclamide and lornoxicam in Chinese subjects

    摘要
  • 摘要: 目的研究人体内细胞色素P450 2C9酶突变等位基因CYP2C9*3对格列本脲和氯诺昔康药代动力学的影响。方法采用PCR-RFLP方法对83名无血源关系的受试者进行CYP2C9*3等位基因的筛查，基因型为CYP2C9*1/*3(n=7)和*1/*1(n=11)的受试者分别参加了格列本脲和氯诺昔康的人体药代动力学试验。采用LC/MS/MS法分别测定受试者口服格列本脲(2.5 mg)和氯诺昔康(8 mg)后不同时刻血浆中格列本脲和氯诺昔康的浓度。结果两组受试者口服格列本脲后，CYP2C9*1/*3组AUC0-∞显著增加，为CYP2C9*1/*1组的1.5倍，CL/F降低了40%；两组受试者口服氯诺昔康后，CYP2C9*1/*3组AUC0-∞亦显著增加，为CYP2C9*1/*1组的2.2倍，CL/F降低了55%。结论CYP2C9酶的突变等位基因CYP2C9*3对格列本脲和氯诺昔康的药代动力学有显著性影响。

     

    Abstract: AimTo investigate the impact of CYP2C9*3 on the pharmacokinetics of glibenclamide and lornoxicam. MethodsCYP2C9*3 was measured in 83 non-related Chinese subjects by PCR-RFLP. The pharmacokinetics of lornoxicam and glibenclamide were investigated in 18 subjects (7 with CYP2C9*1/*3 genotype and 11 with *1/*1 genotype). Glibenclamide and lornoxicam in plasma were determined by the sensitive liquid chromatography-tandem mass spectrometry, separately. ResultsAfter a single oral dose of 2.5 mg glibenclamide, Cmax was (70.0±11.5) μg·L-1 in CYP2C9*1/*3 subjects and (51.9±12.3) μg·L-1 in *1/*1 subjects. AUC0-∞ were (435±47) vs (287±95) μg·h·L-1 (in *1/*3 vs *1/*1 subjects), and CL/F were (96±9.3) vs (160±51) mL·min-1, respectively. Statistic analysis results indicated that glibenclamide AUC0-∞ was significantly higher (1.5-fold) and subsequently CL/F was significantly lower (40%) in CYP2C9*1/*3 subjects than those in *1/*1 subjects (P<0.01). After a single oral dose of 8 mg lornoxicam, Cmax was (1.54±0.24) mg·L-1 in CYP2C9*1/*3 subjects and (1.19±0.37) mg·L-1 in *1/*1 subjects. AUC0-∞ were (14.9±2.2) vs (6.92±1.48) mg·h·L-1 (in *1/*3 vs *1/*1 subjects), and CL/F were (9.1±1.2) vs (20.1±4.6) mL·min-1, respectively. Statistic analysis results indicated that lornoxicam AUC0-∞ was significantly higher (2.2-fold) and subsequently CL/F was significantly lower (55%) in CYP2C9*1/*3 subjects than those in *1/*1 subjects (P<0.001). ConclusionCYP2C9*3 greatly affects both the pharmacokinetic profiles of glibenclamide and lornoxicam. The elimination of these drugs significantly decreased in subjects with CYP2C9*1/*3 genotype, especially lornoxicam.

     

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