Pharmacokinetics of losartan, an angiotensin II receptor antagonist, and its active metabolite EXP3174 in humans
Pharmacokinetics of losartan, an angiotensin II receptor antagonist, and its active metabolite EXP3174 in humans
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DOI：
10.1016/0009-9236(95)90020-9
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发表时间：
1995-12-01
影响因子：
6.7
通讯作者：
Bjornsson, TD
中科院分区：
文献类型：
--
作者：
Lo, MW;Goldberg, MR;Bjornsson, TD
在18名健康男性受试者中，对静脉注射氯沙坦、静脉注射EXP 3174和口服氯沙坦后血管紧张素II受体拮抗剂氯沙坦钾及其活性羧酸代谢产物EXP 3174的药代动力学进行了表征。在这些受试者中，氯沙坦的平均血浆清除率为610 ml/min，分布容积为34 L。肾脏清除率（70 ml/min）占血浆清除率的12%。终末半衰期为2.1小时。相比之下，EXP 3174的平均血浆清除率为47 ml/min，分布容积为10 L。肾脏清除率为26 ml/min，占血浆清除率的55%;终末半衰期为6.3小时。氯沙坦口服后1h达峰。在3 1/2小时内达到EXP 3174的峰浓度。EXP 3174的血药浓度-时间曲线下面积约为氯沙坦的4倍。氯沙坦片的口服生物利用度为33%。生物利用度低主要是由于首过代谢。氯沙坦静脉或口服给药后，氯沙坦转化为代谢产物EXP 3174的转化率为14%。
The pharmacokinetics of the angiotensin II receptor antagonist losartan potassium and its active carboxylic acid metabolite EXP3174 were characterized in 18 healthy male subjects after administration of intravenous losartan, intravenous EXP3174, and oral losartan. In these subjects, the average plasma clearance of losartan was 610 ml/min, and the volume of distribution was 34 L. Renal clearance (70 ml/min) accounted for 12% of plasma clearance. Terminal half-life was 2.1 hours. In contrast, the average plasma clearance of EXP3174 was 47 ml/min, and its volume of distribution was 10 L. Renal clearance was 26 ml/min, which accounted for 55% of plasma clearance; terminal half-life was 6.3 hours. After oral administration of losartan, peak concentrations of losartan were reached in 1 hour. Peak concentrations of EXP3174 were reached in 3 1/2 hours. The area under the plasma concentration-time curve of EXP3174 was about four times that of losartan. The oral bioavailability of losartan tablets was 33%. The low bioavailability was mainly attributable to first-pass metabolism. After intravenous or oral administration of losartan the conversion of losartan to the metabolite EXP3174 was 14%.