The Pharmacokinetics and Pharmacodynamics of Losartan in Continuous Ambulatory Peritoneal Dialysis

The pharmacokinetics and pharmacodynamics of losartan and its active metabolite, E‐3174, were studied in 8 stable, hypertensive continuous ambulatory peritoneal dialysis (CAPD) patients. Following a 1‐week washout period, subjects received 100 mg of losartan orally for 7 days. On Days 1 and 7, hemodynamic and hormonal responses were determined, as were PK parameters on Day 7. Peritoneal equilibration testing was performed pre‐ Day 1 and on Day 7. AUC 0–24 and t 1/2 for losartan and E‐3174 were 95 ± 49.9μg•min/mL and 176 ± 82.1 μg•min/mL and 172.5 ± 86.7 minutes and 628 ± 575 minutes, respectively. These volues are similar to those of normal subjects and subjects on hemodialysis. Peritoneal clearance of losartan and E‐3174 was negligible. All subjects demonstrated a substantial reduction in blood pressure with at least a 10 mmHg drop in diastolic BP. Plasma renin activity (PRA) values increased, but aldosterone, endothelin, norepinephrine, and epinephrine values did not change following 7 days of losartan. Losartan was well tolerated in all study subjects.