Spirapril is a non-sulfhydryl
angiotensin converting enzyme (
ACE) inhibitor 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 > or = 6 mg once daily produced reductions in blood pressure of approximately 10 to 18 mm Hg (systolic) and 7 to 13 mm Hg (diastolic) [24-hour postdose trough readings at the end of the treatment period]. Blood pressure normalisation (trough diastolic blood pressure < or = 90 mm Hg) had occurred in 29 to 50% of patients at the end of these investigations. The dose-response curve for
spirapril appears to be flat for doses of 6 to 24 mg once daily. Comparisons with other
ACE inhibitors 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 produced similar reductions in blood pressure to those seen with
enalapril or
captopril. When given as monotherapy or in combination with
hydrochlorothiazide,
spirapril may offer potential advantages over the
calcium antagonist
nitrendipine.
Spirapril is generally well tolerated and produces an adverse event profile similar to that of other
ACE inhibitors. 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 contrast to most
ACE inhibitors, which are eliminated by a predominantly renal mechanism that results in accumulation of the active metabolite when renal function is impaired. However, the utility of
spirapril in this patient group has yet to be fully determined because of conflicting data regarding its effects on renal function. Thus,
spirapril is an effective
antihypertensive agent which is well tolerated. Further comparative trials are needed to fully determine its efficacy with respect to other
ACE inhibitors, and a better understanding of its effects on renal function will clarify its role in hypertensive patients with
renal failure.