Alacepril: an effective antihypertensive agent

Six patients with severe essential hypertension (WHO stage III or diastolic BP > 115mm Hg) received a single dose of the antihypertensive alacepril [DU-1219; Dainippon] 12.5mg orally and were assessed for up to 24 hours. Plasma concentrations of free and total captopril were also determined, since alacepril is converted to captopril in vivo. The patients then received alacepril 12.5mg (n = 4), 6.2Smg (1) or 25mg (1) for 7-14 days.

The mean BP was significantly reduced during the 24 hours from a baseline value of 126mm Hg to a minimum value at 6 hours of 95mm Hg (single dose) and 97mm Hg (consecutive dose). The peak plasma concentrations of free captopril for the single and consecutive studies were 28.3 and 40.3 ng/ml, respectively, and time to reach peak concentration was 2.5 hours for both studies. Respective values for total captopril were 151.7 ng/ml and 3.3 hours for the single dose and 187.2 ng/ml and 3.0 hours for the consecutive doses. The AUCs for free captopril were 185.9 and 410.8 ng' hour/ml, respectively, for single and consecutive doses and for total captopril were 1699.1 and 1804.7 ng' hour/ml, respectively. The elimination half-life of total captopril was 7.9 hours for both studies. Urinary excretions of free and total captopril in the consecutive study were 36.6 and 39.8"10 of the dose, respectively. There was a significant reduction in plasma ACE activity for up to 8 hours in both studies, and this was significantly correlated with the decrease in mean BP. A significant increase in plasma renin activity (for up to

4 hours) and in angiotensin I concentration were also found . However, there were no significant changes in plasma aldosterone and cortisol concentrations, and no symptomatic side effects reported.

In conclusion , alacepril showed high tolerability and antihypertensive efficacy in the treatment of patients with severe essential hypertension. Shinoiri. H.; Miyizaki, N.; Yasuda, G. ; Miyakawa, T. , Takasaki. I. et a/.: Current Therapeutic Research 38. 537·547 (Oct 1985)

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