After intravenous administration, fosinoprilat was eliminated approximately equally by the liver and kidney. After oral administration of radiolabeled fosinopril, approximately half of the absorbed dose is excreted in the urine and the remainder is excreted in the feces. In two studies involving healthy subjects, the mean body clearance of intravenous fosinoprilat was between 26 and 39 mL/min.

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 t_1/2 for accumulation of fosinoprilat averaged 11.5 hours. In patients with heart failure, the effective t_1/2 was 14 hours.

In patients with mild-to-severe renal insufficiency (creatinine clearance 10–80 mL/ min/1.73m²), 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/1.73 m²), 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 peritoneal 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.

In elderly (male) subjects (65-74 years old) with clinically normal renal and hepatic function, there appear to be no significant differences in pharmacokinetic parameters for fosinoprilat compared to those of younger subjects (20-35 years old).

In pediatric patients, (N=20) age 6 to 16 years, with glomerular filtration rate ≥ 25 mL/min, given a single dose of fosinopril (0.3 mg/kg given as solution), the mean AUC and Cmax values of fosinoprilat (the active form of fosinopril) were similar to those seen in healthy adults receiving 20 mg (about 0.3 mg/kg for a 70 kg adult) of fosinopril as a solution. The terminal elimination half-life of fosinoprilat in pediatric patients was 11-13 hours, also similar to that observed in adults.

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.

Hypertension

Adult

Administration of MONOPRIL (fosinopril sodium tablets) to patients with mild-to- moderate hypertension results in a reduction of both supine and standing blood pressure to about the same extent with no compensatory tachycardia. Symptomatic postural hypotension is infrequent, although it can occur in patients who are salt- and/or volume-depleted (see WARNINGS). Use of MONOPRIL in combination with thiazide diuretics gives a blood pressure-lowering effect greater than that seen with either agent alone.

Bookmark this page: