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Pharmacokinetics of intravenous and oral losartan in patients with heart failure

MW Lo, J Toh, SE Emmert, MA Ritter, CI Furtek, H Lu, WS Colucci, BF Uretsky, and E Rucinska

The pharmacokinetics of a selective AT1-subtype, nonpeptide, orally active, angiotensin II receptor antagonist, losartan, were characterized in 11 patients with heart failure (New York Heart Association class II, n = 6; class III, n = 4; class IV, n = 1) after oral and intravenous administration. In these patients, average plasma clearance of losartan was 566 mL/min, volume of distribution at steady-state was 34 L, and terminal plasma half-life was 1.5 hours. Average bioavailability was 36%. No clinically significant accumulation of losartan or its active metabolite, EXP3174, occurred after multiple-dose oral administration for 7 to 8 days. Terminal plasma half-life of EXP3174 after oral administration of losartan was 7.6 hours. The pharmacokinetics of losartan in patients in this study appear to be similar to those in healthy subjects studied previously.
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