SPIRAPRIL - A PRELIMINARY REVIEW OF ITS PHARMACOLOGY AND THERAPEUTIC EFFICACY IN THE TREATMENT OF HYPERTENSION (REPRINTED FROM DRUGS, VOL 49, 1995)

Spirapril is a non-sulfhydryl angiotensin converting enzyme (ACE) inhi bitor prodrug which is converted to the active metabolite spiraprilat following oral administration, and which has been evaluated primarily for the treatment of hypertension. In dose-finding studies of patients with mild to severe hypertension, spirapril greater than or equal to 6 mg once daily produced reductions in blood pressure of approximately 10 to 18 mmHg (systolic) and 7 to 13 mmHg (diastolic) [24-hour postdo se trough readings at the end of the treatment period]. Blood pressure normalisation (trough diastolic blood pressure less than or equal to 90 mmHg) had occurred in 29 to 50% of patients at the end of these inv estigations. The dose-response curve for spirapril appears to be flat for doses of 6 to 24mg once daily. Comparisons with other ACE inhibito rs are limited in number, and further studies are required before the relative antihypertensive efficacy of spirapril can be fully evaluated . However, in single, well controlled clinical trials, spirapril produ ced similar reductions in blood pressure to those seen with enalapril or captopril. When given as monotherapy or in combination with hydroch lorothiazide, spirapril may offer potential advantages over the calciu m antagonist nitrendipine. Spirapril is generally well tolerated and p roduces an adverse event profile similar to that of other ACE inhibito rs. Data from small studies suggest that spirapril can be used without dosage adjustment in patients with renal impairment, as a consequence of its dual renal and hepatic clearance mechanisms. This is in contra st to most ACE inhibitors, which are eliminated by a predominantly ren al mechanism that results in accumulation of the active metabolite whe n renal function is impaired. However, the utility of spirapril in thi s patient group has yet to be fully determined because of conflicting data regarding its effects on renal function. Thus, spirapril is an ef fective antihypertensive agent which is well tolerated. Further compar ative trials are needed to fully determine its efficacy,vith respect t o other ACE inhibitors, and a better understanding of its effects on r enal function will clarify its role in hypertensive patients with rena l failure.