Document Detail

The pharmacokinetics of losartan in renal insufficiency.
MedLine Citation:
PMID:  18800456     Owner:  NLM     Status:  MEDLINE    
AIM: To determine the effect of renal insufficiency on the pharmacokinetics and pharmacodynamics of losartan (MK-954) and its metabolite E3174. PATIENTS AND METHODS: A two-center, unblinded trial was performed in 18 patients (age range 31-63 years) with various degrees of renal function grouped according to the renal clearance of creatinine: group I, creatinine clearance > or = 75 ml/min; group II, creatinine clearance 30-74 ml/min; group III, creatinine clearance 10-29 ml/min (n = 6 in all groups). Losartan (100 mg/day) was administered under supervised conditions for seven consecutive days. Plasma samples were taken for up to 60 h and 24-h urine collections were made following the final dose of losartan (on day 7) to determine losartan and E3174 concentrations, with simultaneous measurements of blood pressure and the pulse rate. RESULTS: The pharmacokinetic parameters for losartan and E3174 changed inconsequentially across the range of renal insufficiency. For losartan, renal clearance decreased from 50 +/- 19 ml/min in group I to 2.3 +/- 0.9 ml/min in group III (P < 0.05). For E3174, although the renal clearance decreased from 16 +/- 4.1 ml/min in group I to 1.3 +/- 0.8 ml/min in group III (P < 0.05), the area under the plasma concentration curve did not change. CONCLUSIONS: The steady-state areas under the curve of losartan and E3174 are not significantly changed with renal impairment. The renal clearance of losartan decreases with renal impairment but since only a small percentage of the dose is ordinarily eliminated by the kidney, the demonstrated reduction in clearance is clinically irrelevant. The renal clearance of E3174 also decreases with renal impairment, but the steady-state area under the curve does not increase with increasing degrees of renal insufficiency. These pharmacokinetic alterations do not warrant dose adjustment in the face of renal insufficiency.
D A Sica; M W Lo; W C Shaw; W F Keane; T W Gehr; C E Halstenson; K Lipschutz; C I Furtek; M A Ritter; S Shahinfar
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Publication Detail:
Type:  Clinical Trial; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension. Supplement : official journal of the International Society of Hypertension     Volume:  13     ISSN:  0952-1178     ISO Abbreviation:  J Hypertens Suppl     Publication Date:  1995 Jul 
Date Detail:
Created Date:  2008-09-19     Completed Date:  2008-10-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8501422     Medline TA:  J Hypertens Suppl     Country:  England    
Other Details:
Languages:  eng     Pagination:  S49-52     Citation Subset:  IM    
Division of Clinical Pharmacology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0160, USA.
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MeSH Terms
Antihypertensive Agents / pharmacokinetics*
Area Under Curve
Blood Pressure / drug effects,  physiology
Creatinine / blood,  urine
Dose-Response Relationship, Drug
Heart Rate / drug effects,  physiology
Imidazoles / blood,  pharmacokinetics,  urine
Losartan / blood,  pharmacokinetics*,  urine
Middle Aged
Renal Insufficiency / metabolism*
Tetrazoles / blood,  pharmacokinetics,  urine
Reg. No./Substance:
0/Antihypertensive Agents; 0/Imidazoles; 0/Tetrazoles; 114798-26-4/Losartan; 124750-92-1/EXP3174; 60-27-5/Creatinine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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