FOSINOPRIL - CLINICAL PHARMACOKINETICS AND CLINICAL POTENTIAL

Fosinopril is a phosphorus-containing ester prodrug of an angiotensin- converting enzyme (ACE) inhibitor. It is hydrolysed mainly in the gast rointestinal mucosa and liver to the active diacid, fosinoprilat, whic h has unique pharmacological properties. The majority of the active mo ieties of other ACE inhibitors are excreted in the urine. This means t hat an adjustment in either the dosage and/or the administration inter val is needed in patients with moderate to severe renal dysfunction, i n order to reduce drug accumulation and the possibility of an excessiv e decrease in blood pressure or other adverse effects. On the other ha nd, fosinoprilat is excreted both in urine and bile (as with temocapri lat, zofenoprilat and spiraprilat), and thus an adjustment of dosage a nd/or administration interval may be unnecessary in patients with mode rate to severe renal dysfunction, as impaired renal function influence s little of the pharmacokinetics of fosinoprilat. Furthermore, the ava ilable evidence suggests that the pharmacokinetic variables of fosinop rilat in patients receiving haemodialysis were similar to those in pat ients with moderate to severe renal dysfunction. Dosage modifications or supplemental dose administration following dialysis may be unnecess ary. The hypotensive effect of the combination of fosinopril and a diu retic 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 ventri cular hypertrophy because it produces an adequate reduction in blood p ressure and reversal of left ventricular hypertrophy. There are a larg e number of studies of the pharmacokinetics of fosinopril. However stu dies of its pharmacokinetic drug interactions with other drugs are far fewer. Further investigations are needed in several clinical settings .