中国临床药学杂志2005，Vol.14Issue(6)：327-331,5.
LC-MS/MS法测定甲氯噻嗪血浓度及药动学研究
Study of pharmacokinetics and LC-MS/MS method of blood concentration of methyclothiazide
李雪宁 1陈伟力 1徐红蓉 1李志善1
作者信息
- 1. 复旦大学附属中山医院国家药品临床研究基地,上海,200032
- 折叠
摘要
Abstract
AIM To evaluate the safety and pharmacokinetic parameters of a domestic methyclothiazide tablet in Chinese healthy male volunteers after administered three different oral dosage. METHODS Ten healthy Chinese volunteers were given a different single oral dosage domestic methyclothiazide tablet. The concentration of methyclothiazide in blood plasma was measured by an validated LC-MS/MS method and were assessed with non-compartment model to obtain the pharmacokinetic parameters. RESULTS The pharmacokinetic parameters of methyclothiazide tablet for orally administered different dosage (2.5,5.0,10mg) were as follows: AUC0→t: (128.40 ± 20.88), (257.68 ± 37.10) and (517.27 ±119.17)μg·h· L-1; AUC0→∞: (150.47 ± 24.78), (299.52 ± 45.56) and (602.57 ± 129.67)μg· h·L-1; cmax:(8.43 ± 2.21) ,(16.60±2.53) and (32.08 ± 8.44)μg·L-1; tmax:(2.60 ± 0.70) ,(2.30 ± 0.95) and (3.25 ± 1.27)h;T1/2:(17.63 ± 2.61), (17.37 ± 2.62) and (17.87 ± 2.49)h; Ka: (1. 195 ± 0.720), (1.352 ± 0.626) and(1.221± 1.152) h-1;Ke: (0.0344 ± 0.1050),(0.0391 ± 0.0103) and (0.0362 ±0.0081) h-1; Vd: (236.36 ±69.20), (221.79 ± 87.94) and (299.30 ± 204.72) L;CL: (0.0174 ± 0.0039), (0.0178 ± 0.0035) and (0.0179 ±0.0036) L· h-1. CONCLUSION The results show that there was a good linear in AUC0→t (r = 1 ) and cmax (r =0.999 8) in dosage range of 2.5-10 mg. There is no significant difference in tmax and T1/2 between three different dosage groups (SPSS 10.0). The geometric mean of AUC0→t and cmax after dose is rectified are 50.69,51.04,50.39 μg·h·L-1and 3.26,3.28,3.06 μg· L- 1, respectively. No any adverse drug reactions are found during the whole study.关键词
甲氯噻嗪/LC-MS/MS法/药动学Key words
methyclothiazide/LC-MS/MS/pharmacokinetics分类
医药卫生引用本文复制引用
李雪宁,陈伟力,徐红蓉,李志善..LC-MS/MS法测定甲氯噻嗪血浓度及药动学研究[J].中国临床药学杂志,2005,14(6):327-331,5.
