Overview of Fosinopril

Summary

Fosinopril is a prodrug of the active diacid compound, fosinoprilat. Fosinopril is the first of a new chemical class of angiotensin-converting enzyme (ACE) inhibitors, the phosphinic acids, and is indicated for the once-daily treatment of mild-to-moderate essential hypertension.

Following oral administration, fosinopril effectively lowers systolic and diastolic blood pressure for 24 hours. Short term (8- to 12-week) clinical trials have shown fosinopril 10 to 40mg once daily to be significantly more effective than placebo and comparable to propranolol 40 to 80mg twice daily in the treatment of patients with mild-to-moderate or moderate-to-severe essential hypertension unresponsive to diuretic monotherapy. In a 12-week trial, fosinopril once daily and enalapril once daily produced equivalent antihypertensive effects in patients with mild-to-moderate essential hypertension. In elderly patients with mild-to-moderate hypertension, fosinopril lowered blood pressure as effectively as nifedipine sustained release (SR) and appears to have been better tolerated.

Fosinopril was well tolerated by patients in clinical trials, and the incidence of adverse events was similar to that observed with placebo, propranolol or enalapril. Headache, cough, and dizziness were reported most often, but these symptoms are typical of ACE inhibitors as a class. Fosinopril appears to have a low potential for drug interactions.

The unique characteristic of fosinopril is its dual route of elimination, which is equally balanced between the renal and hepatic routes in patients with normal kidney function. Moreover, there is evidence that in patients with renal dysfunction, a compensatory shift towards increased elimination by the liver takes place, thereby reducing the risk of drug accumulation. This feature distinguishes fosinopril from nearly all long-acting ACE inhibitors, which are eliminated primarily by the kidney and which may require adjustment of the initial dose for varying degrees of renal dysfunction. Fosinopril’s dual compensatory elimination makes it a novel compound suitable for a wide range of hypertensive patients, including elderly patients and those with declining renal function. Dual elimination may also reduce the risk of adverse drug experiences related to drug accumulation and allows a simplified dosing regimen regardless of renal function.