|
In healthy subjects, the terminal elimination half-life (t 1/ 2 ) of an intravenous dose of radiolabeled fosinoprilat is approximately 12 hours. In hypertensive patients with normal renal and hepatic function, who received repeated doses of fosinopril, the effective t1/ 2 for accumulation of fosinoprilat averaged 11.5 hours. In patients with heart failure, the effective t1/ 2 was 14 hours. In patients with mild-to-severe renal insufficiency (creatinine clearance 10Ð 80 mL/ min/ 1.73m 2 ), the clearance of fosinoprilat does not differ appreciably from normal, because of the large contribution of hepatobiliary elimination. In patients with end-stage renal disease (creatinine clearance < 10 mL/ min/ 1.73m 2 ), the total body clearance of fosinoprilat is approximately one-half of that in patients with normal renal function. (See DOSAGE AND ADMINISTRATION.) Fosinopril is not well dialyzed. Clearance of fosinoprilat by hemodialysis and peri-toneal dialysis averages 2% and 7%, respectively, of urea clearances. In patients with hepatic insufficiency (alcoholic or biliary cirrhosis), the extent of hydrolysis of fosinopril is not appreciably reduced, although the rate of hydrolysis may be slowed; the apparent total body clearance of fosinoprilat is approximately one-half of that in patients with normal hepatic function. Text Continues Below
In elderly (male) subjects (65-74 years old) with clinically normal renal and hepatic function, there appear to be no significant differences in pharmacokinetic parame-ters for fosinoprilat compared to those of younger subjects (20-35 years old). Fosinoprilat was found to cross the placenta of pregnant animals. Studies in animals indicate that fosinopril and fosinoprilat do not cross the blood-brain barrier. Pharmacodynamics and Clinical Effects Serum ACE activity was inhibited by 90% at 2 to 12 hours after single doses of 10 to 40 mg of fosinopril. At 24 hours, serum ACE activity remained suppressed by 85%, 93%, and 93% in the 10, 20, and 40 mg dose groups, respectively. Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
|
.gif)
