Pharmacokinetics and blood pressure response of losartan in end-stage renal disease

Background: Losartan is a selective angiotensin AT(1) receptor antagonist c urrently employed in the management of essential hypertension. This compoun d is in common use in populations with renal failure and end-stage nnal dis ease (ESRD). Objective: To investigate the pharmacokinetics and pharmacodynamics of losa rtan in patients with ESRD in order to establish administration guidelines. Methods: Patients were administered losartan 100 mg/day for 7 days, and aft er the seventh and final dose pharmacokinetic parameters were determined fo r both losartan and its active metabolite E-3174. During the study, the hae modialytic clearances of losartan and E-3174 were measured during a standar d 4-hour dialysis session. Neurohumoral and biochemical changes were assess ed during losartan administration. Results: The pharmacokinetics of losartan and E-3174 in haemodialysis patie nts did not alter to a clinically significant level. Losartan administratio n was accompanied by a decline in plasma aldosterone level as well as by an increase in plasma renin activity. Losartan administration resulted in a d ecline in plasma uric acid level, despite the fact that the study participa nts had no residual renal function. Losartan and E-3174 were not dialysable . Conclusions: The pharmacokinetics of losartan and E-3174 are minimally alte red in ESRD; thus, dosage adjustment is not required in the presence of adv anced dialysis-dependent renal failure. In addition, postdialysis supplemen tation is not required for losartan because of the negligible dialysability of losartan and E-3174.