PHARMACOKINETICS OF INTRAVENOUS AND ORAL LOSARTAN IN PATIENTS WITH HEART-FAILURE

The pharmacokinetics of a selective AT(1)-subtype, nonpeptide, orally active, angiotensin II receptor antagonist, losartan, were characteriz ed 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 intraven ous administration. In these patients, average plasma clearance of los artan 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 act ive metabolite, EXP3174, occurred after multiple-dose oral administrat ion for 7 to 8 days. Terminal plasma half-life of EXP3174 after oral a dministration of losartan was 7.6 hours. The pharmacokinetics of losar tan in patients in this study appear to be similar to those in healthy subjects studied previously. Journal of Clinical Pharmacology, 1998;3 8:525-532 (C) 1998 The American College of Clinical Pharmacology.