Fosinopril: Pharmacokinetics and pharmacodynamics in congestive heart failure*

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Abstract
Fosinoprilat, the active product of fosinopril, is eliminated by a hepatic pathway, in addition to the renal pathway shared by other angiotensin converting enzyme inhibitors. Congestive heart failure (CHF) may elevate drug plasma concentrations caused by a reduction in steady‐state volume of distribution (Vss) and/or an impairment of clearance. This study compared the pharmacokinetics and pharmacodynamics of fosinopril (intravenous and oral) in 10 patients with established CHF and 10 age‐, sex‐, and weight‐matched normal control subjects. There were no statistically significant differences between the patients with CHF and the control patients with respect to maximum drug concentration (Cmax) or area under the plasma concentration‐time curve from 0 to infinity. Absolute bioavailability was approximately 29%. Vss was similar, and protein binding was 99% in both groups. The oral half‐life of fosinoprilat was significantly longer than the intravenous half‐life for both the patients with CHF and normal subjects, without statistically significant differences between the study groups. Median time to reach Cmax occurred at 4 hours in each group and corresponded to maximum angiotensin converting enzyme inhibition, which was essentially complete through 12 hours and markedly reduced through 24 hours. Thus these data indicate that patients with CHF can receive fosinopril without undue increases in fosinoprilat concentrations. This probably is due to the dual excretory pathways.