Pharmacokinetics and Blood Pressure Response of Losartan in End-Stage Renal Disease
作者:
Domenic A. Sica,
Charles E. Halstenson,
Todd W.B. Gehr,
William F. Keane,
期刊:
Clinical Pharmacokinetics
(ADIS Available online 2000)
卷期:
Volume 38,
issue 6
页码: 519-526
ISSN:0312-5963
年代: 2000
出版商: ADIS
关键词: Angiotensin antagonists, pharmacokinetics;E 3174, pharmacokinetics;Losartan, pharmacodynamics;Losartan, pharmacokinetics;Renal failure;Research and development
数据来源: ADIS
摘要:
BackgroundLosartan is a selective angiotensin AT1receptor antagonist currently employed in the management of essential hypertension. This compound is in common use in populations with renal failure and end-stage renal disease (ESRD).ObjectiveTo investigate the pharmacokinetics and pharmacodynamics of losartan in patients with ESRD in order to establish administration guidelines.MethodsPatients were administered losartan 100 mg/day for 7 days, and after the seventh and final dose pharmacokinetic parameters were determined for both losartan and its active metabolite E-3174. During the study, the haemodialytic clearances of losartan and E-3174 were measured during a standard 4-hour dialysis session. Neurohumoral and biochemical changes were assessed during losartan administration.ResultsThe pharmacokinetics of losartan and E-3174 in haemodialysis patients did not alter to a clinically significant level. Losartan administration was accompanied by a decline in plasma aldosterone level as well as by an increase in plasma renin activity. Losartan administration resulted in a decline in plasma uric acid level, despite the fact that the study participants had no residual renal function. Losartan and E-3174 were not dialysable.ConclusionsThe pharmacokinetics of losartan and E-3174 are minimally altered in ESRD; thus, dosage adjustment is not required in the presence of advanced dialysis-dependent renal failure. In addition, postdialysis supplementation is not required for losartan because of the negligible dialysability of losartan and E-3174.
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