Fosinopril: Clinical pharmacokinetics and clinical potential

• Published in: Clinical pharmacokinetics Vol. 32; no. 6; pp. 460 - 480
• Main Authors: SHIONOIRI, H, NARUSE, M, MINAMISAWA, K, UEDA, S, HIMENO, H, HIROTO, S, TAKASAKI, I
• Format: Journal Article
• Language: English
• Published: Auckland Adis international 01-06-1997
• Subjects: Absorption; Angiotensin-Converting Enzyme Inhibitors - pharmacokinetics; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensive agents; Antihypertensive Agents - pharmacokinetics; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Cardiovascular system; Drug Interactions; Female; Fosinopril - pharmacokinetics; Fosinopril - pharmacology; Fosinopril - therapeutic use; Heart Failure - drug therapy; Heart Failure - metabolism; Hemodynamics - drug effects; Humans; Hypertension - drug therapy; Hypertension - physiopathology; Hypertrophy, Left Ventricular - drug therapy; Hypertrophy, Left Ventricular - metabolism; Kidney - metabolism; Kidney Diseases - metabolism; Kidney Diseases - physiopathology; Liver - metabolism; Liver Diseases - metabolism; Liver Diseases - physiopathology; Male; Medical sciences; Myocardial Ischemia - drug therapy; Myocardial Ischemia - metabolism; Peritoneal Dialysis, Continuous Ambulatory; Pharmacology. Drug treatments; Renal Dialysis; Kidney disease; Human; Heart failure; Urinary system disease; Hemodialysis; Indication; Use; Hepatic disease; Review; Biological activity; Liver failure; Renal failure; Digestive diseases; Antihypertensive agent; Fosinopril; Drug interaction; Hemodynamics; Pharmacokinetics; ACE inhibitor
• ISSN: 0312-5963; 1179-1926
• DOI: 10.2165/00003088-199732060-00003

Fosinopril is a phosphorus-containing ester prodrug of an angiotensin-converting enzyme (ACE) inhibitor. It is hydrolysed mainly in the gastrointestinal mucosa and liver to the active diacid, fosinoprilat, which has unique pharmacological properties. The majority of the active moieties of other ACE inhibitors are excreted in the urine. This means that an adjustment in either the dosage and/or the administration interval is needed in patients with moderate to severe renal dysfunction, in order to reduce drug accumulation and the possibility of an excessive decrease in blood pressure or other adverse effects. On the other hand, fosinoprilat is excreted both in urine and bile (as with temocaprilat, zofenoprilat and spiraprilat), and thus an adjustment of dosage and/or administration interval may be unnecessary in patients with moderate to severe renal dysfunction, as impaired renal function influences little of the pharmacokinetics of fosinoprilat. Furthermore, the available evidence suggests that the pharmacokinetic variables of fosinoprilat in patients receiving haemodialysis were similar to those in patients with moderate to severe renal dysfunction. Dosage modifications or supplemental dose administration following dialysis may be unnecessary. The hypotensive effect of the combination of fosinopril and a diuretic is synergistic. Pharmacokinetic interactions with fosinopril are unlikely in patients receiving thiazide or loop diuretics. Fosinopril has beneficial effects for patients with hypertension and left ventricular hypertrophy because it produces an adequate reduction in blood pressure and reversal of left ventricular hypertrophy. There are a large number of studies of the pharmacokinetics of fosinopril. However studies of its pharmacokinetic drug interactions with other drugs are far fewer. Further investigations are needed in several clinical settings.