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Drug concentration response relationships in normal volunteers after oral administration of losartan, an angiotensin II receptor antagonist
Author(s) -
Munafo Alain,
Christen Yves,
Nussberger Jürg,
Shum Linyee Y,
Borland R Michael,
Lee Robert J,
Waeber Bernard,
Biollaz Jérôme,
Brunner Hans R
Publication year - 1992
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1992.56
Subject(s) - losartan , angiotensin ii , active metabolite , angiotensin ii receptor antagonist , blockade , losartan potassium , renin–angiotensin system , pharmacology , endocrinology , metabolite , medicine , oral administration , antagonist , chemistry , blood pressure , receptor
The aim of this study was to investigate the relationships between plasma concentrations of losartan, an orally active angiotensin II inhibitor, its active metabolite EXP3174, and angiotensin II blockade. Six healthy subjects received single oral doses of 40, 80, or 120 mg losartan and placebo at 1‐week intervals in a crossover study. Angiotensin II blockade was assessed by the blood pressure response to exogenous angiotensin II before and after losartan administration. EXP3174 reached higher plasma concentrations and was eliminated more slowly than its parent compound; its levels paralleled the profile of angiotensin II blockade closer than losartan. Inhibition of the pressure response was dose dependent. The Hill‐shaped relationship between response and EXP3174 concentration (or time‐integrated variables) approached a plateau with 80 mg. The dose‐dependent increase in plasma renin and angiotensin II exhibited a considerable individual scatter. We conclude that losartan produces a dose‐dependent, effective angiotensin II blockade that is largely determined by the active metabolite EXP3174. Clinical Pharmacology and Therapeutics (1992) 51 , 513–521; doi: 10.1038/clpt.1992.56