Overview of Fosinopril
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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.
KeywordsNifedipine Enalapril Essential Hypertension Lisinopril Drug Invest
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- Cirillo VJ, Till AE, Gomez HJ, et al. Effect of age on lisinopril pharmacokinetics. (Abstract). Clinical Pharmacology and Therapeutics 39: 187, 1986Google Scholar
- Clementy J. Double-blind, randomised study of fosinopril versus nifedipine SR in the treatment of mild-to-moderate hypertension in elderly patients. Drug Investigation 3 (Suppl. 4): 45–53, 1991Google Scholar
- Creasey WA, Brennan J, McKinstry DN, Fordtran JS. Absorption of fosinopril from various sites within the gastrointestinal tract. Acta Pharmacologica et Toxicologica 59 (Suppl. 5): 83, 1986Google Scholar
- Duchin K, Tu J, Frantz M, et al. Pharmacodynamics and pharmacokinetics of SQ 28.555 (SQ), a new angiotensin-converting enzyme inhibitor, in healthy subjects. (Abstract.) Clinical Pharmacology and Therapeutics 37: 192, 1985Google Scholar
- Fruncillo RJ, Rocci ML, Vlasses PH, et al. Disposition of enalapril and enalaprilat in renal insufficiency. Kidney International 31 (Suppl. 20): 117–122, 1987Google Scholar
- Goldstein RJ. A multicentre randomised double-blind parallel comparison of fosinopril sodium and enalapril maleate for the treatment of mild-to-moderate essential hypertension. Drug Investigation 3 (Suppl. 4): 38–44, 1991Google Scholar
- Horvath AM, Olsen SC, Ferry JJ, et al. Pharmacokinetics of quinapril and its active metabolite, quinaprilat, in patients with renal insufficiency. Journal of Clinical Pharmacology 28: 918, 1988Google Scholar
- Levinson B, Sugarman AA, Couchman T, et al. Advanced age per se has no influence on the kinetics of the active diacid of fosinopril. Journal of Clinical Pharmacology 26: 555, 1986Google Scholar
- Macdonald NJ, Elliott HL, Howie CH, et al. Age and the pharmacodynamics and pharmacokinetics of benazepril. British Journal of Clinical Pharmacology 27 (Suppl.): 707P–708P, 1988Google Scholar
- MacLeod CM, Bartley EA, Kripalani KJ, Marino MR. Effect of hepatic function on disposition of fosinopril in humans. Abstract. Journal of Clinical Pharmacology 30: 839, 1990Google Scholar
- Miller WE. Randomised, double-blind, comparison of fosinopril and propranolol added to diuretic therapy for the treatment of moderate-to-severe hypertension. Drug Investigation 3 (Suppl. 4): 32–37, 1991Google Scholar
- Ondetti MA. Structural relationships of angiotensin-converting enzyme inhibitors to pharmacologic activity. Circulation 77 (Suppl. 1): 174–178, 1988Google Scholar
- Oren S, Messerli FH, Grossman E, Garavaglia GE, Frohlich ED. Intermediate and short-term cardiovascular effects of fosinopril, a new angiotensin-converting-enzyme inhibitor, in patients with essential hypertension. Journal of the American College of Cardiology 17: 1183–1187, 1991PubMedCrossRefGoogle Scholar
- Perindopril (Coversyl) product monograph, Adis Press 15, 1989Google Scholar
- Ward TD. The additive effect of fosinopril in patients taking chlorthalidone for the treatment of mild-to-moderate essential hypertension: a multicentre, placebo-controlled, dose-response study. Drug Investigation 3 (Suppl. 4): 25–31, 1991Google Scholar
- Zusman RM, Christensen DM, Higgins J, et al. Fosinopril improves left ventricular systolic and diastolic function. Clinical Research 38: 554A, 1990Google Scholar