Nonpeptide Angiotensin II Receptor Antagonist: Pharmacokinetics and Pharmacodynamics in Rats of EXP3174, an Active Metabolite of Losartan
作者:
Pancras C. Wong,
David D. Christ,
Nancy Wong,
Gilbert N. Lam,
期刊:
Pharmacology
(Karger Available online 1996)
卷期:
Volume 52,
issue 1
页码: 25-29
ISSN:0031-7012
年代: 1996
DOI:10.1159/000139357
出版商: S. Karger AG
关键词: Angiotensin II receptor antagonist;Blood pressure;Hypertension;Losartan;Renin-angiotensin system
数据来源: Karger
摘要:
The pharmacokinetics and pharmacodynamics of EXP3174 {2-n-butyl-4-chloro-1- [(2’-(1H-tetrazole-5-yl)biphenyl-4-yl-)methyl]imidazole-5-carboxylic acid), an angiotensin II receptor antagonist, were studied in conscious rats. Elimination half-life, systemic clearance, and apparent volume of distribution of EXP3174 at a dose of 10 mg/kg i.v. were 2.9 h, 1.8 ml/ min/kg, and 0.25 l/kg, respectively. Inhibition of the angiotensin II pressor response correlated with the log of the steady state plasma EXP3174 concentration in a sigmoidal fashion with an IC50 of about 200 ng/ml. When corrected for plasma protein binding, the IC50 (free) for EXP3174 was 0.4 ng/ml (0.9 nmol/l). This study indicates a predictable plasma concentration-effect relationship of EXP3174 in rats which would be helpful in designing more rational dosing schemes for pharmacodynamic studie
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