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. AUC0-24 and t1/2 for losartan and E-3174 were 95 +/- 49.9 micrograms.min/mL and 176 +/- 82.1 micrograms.min/mL and 172.5 +/- 86.7 minutes and 628 +/- 575 minutes, respectively. These values 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.
Pedro
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AA
Division of Clinical Pharmacology, Medical College of Virginia of Virginia Commonwealth University, Richmond 23298-0160, USA.
Gehr
T W
TW
Brophy
D F
DF
Sica
D A
DA
D000328:Adult; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D003971:Diastole; D005260:Female; D006207:Half-Life; D006801:Humans; D007093:Imidazoles / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000503:physiopathology; D019808:Losartan / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D013599:Systole; D013777:Tetrazoles / Q000097:blood
D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; C066026:losartan carboxylic acid; D019808:Losartan