The pharmacokinetics and pharmacodynamics of losartan in continuous ambulatory peritoneal dialysis

The pharmacokinetics and pharmacodynamics of losartan audits active metabol ite, E-3174, were studied in 8 stable, hypertensive continuous ambulatory p eritoneal dialysis (CAPD) patients. Following a 1-week washout period, subj ects received 100 mg of losartan orally for 7 days. On Days 1 and 7, hemody namic and hormonal responses were determined, as were PK parameters on Day 7. Peritoneal equilibration testing was performed pre-Day 1 and on Day 7.AU C(0-24) and t(1/z) for losartan and E-3174 were 95 +/- 49.9 mu g min/mL and 176 +/- 82.1 mu g.min/mL and 172.5 +/- 86.7 minutes and 628 +/- 575 minute s, respectively. These values are similar to those of normal subjects and s ubjects on hemodialysis. Peritoneal clearance of losartan and E-3174 was ne gligible. All subjects demonstrated a substantial reduction in blood pressu re with at least a 10 mmHg drop in diastolic BT! Plasma renin activity (PRA ) values increased, but aldosterone, endothelin, norepinephrine, and epinep hrine values did not change following 7 days of losartan. Losartan was well tolerated in all study subjects. Journal of Clinical Pharmacology, 2000;40 :389-395 (C)2000 the American College of Clinical Pharmacology.