SINGLE-DOSE AND STEADY-STATE PHARMACOKINETICS OF FOSINOPRIL AND FOSINOPRILAT IN PATIENTS WITH HEPATIC IMPAIRMENT

The single-dose and steady-state pharmacokinetics of the angiotensin-c onverting enzyme (ACE) inhibitor fosinopril and its active diacid, fos inoprilat, were evaluated in 6 healthy volunteers and 12 patients with alcoholic cirrhosis. Fosinopril was administered at a dosage of 10 mg once daily for 14 days. Results in the two groups were similar, with no evidence of accumulation of fosinoprilat in hepatically impaired pa tients. Mean (+/-SD) maximum observed plasma concentrations of fosinop rilat in the healthy subjects were 112.0+/-67.2 ng/mL after the first dose and 144.1+/-61.7 ng/mL at steady-state. Corresponding values for the hepatically impaired patients were 111.4+/-40.1 ng/mL and 140.2+/- 50.9 ng/mL. The area under the serum concentration versus time curve f or healthy volunteers was 790.7+/-431.0 ng.hr/mL after the first dose and 940.3+/-400.4 ng.hr/mL at steady-state. Similar values were noted in hepatically impaired patients: 926.0+/-293.9 ng.hr/mL and 1,255.4+/ -434.0 ng.hr/mL for first dose and steady-state, respectively. No stat istically significant differences were detected in fosinoprilat pharmo cokinetic values between healthy and hepatically impaired subjects. Ab sence of accumulation can be attributed to the dual route of eliminati on of fosinoprilat reported in previous studies. Renal excretion of fo sinoprilat in hepatically impaired patients prevents increased accumul ation. The present findings suggest that the starting dose of fosinopr il used in hypertensive patients with normal renal and hepatic functio n can also be used in patients with hepatic impairment secondary to ci rrhosis.