To assess the efficacy and time-dependent effects of once-daily moexipril, a nonsulfhydryl ester prodrug of the angiotensin-converting enzyme (ACE) inhibitor, moexiprilat, we conducted a multicenter, double-blind, placebo- controlled trial in 51 hypertensive patients using both clinic and ambulatory blood pressure (BP) recordings. Patients were included in the trial based on a minimum of 40% of the daytime diastolic BPs of 90 mm Hg or more during a placebo baseline phase; and the primary endpoint was change in 24-hour ambulatory diastolic BP. Patients were randomized to receive placebo, 7.5 mg of moexipril, or 15 mg of moexipril once daily. Clinic and ambulatory BPs were taken on the first day and after eight weeks of double-blind therapy. After the 7.5-mg dose, there were no significant changes in the acute or prolonged clinic BPs compared with placebo. Compared with adjusted mean changes for placebo, the 150-mg moexipril dose lowered clinic systolic BP, but not diastolic BP. In contrast, acute (1 day) reductions in 24-hour diastolic BPs were -2/-3 mm Hg, -6/-4 mm Hg, and -14/-9 mm Hg on placebo, 7.5 mg of moexipril, and 15 mg of moexipril, respectively (P <.01 for the 15-mg dose). Similarly, after long-term dosing for 8 weeks, reductions in 24-hour diastolic BPs were 1/-2 mm Hg, -6/-4 mm Hg, and -12/-9 mm Hg for the respective treatment groups (P <.01 for the 15-mg dose). Peak effects of the drug occurred approximately 6 hours post dosing, and duration of action based on ambulatory BP monitoring was less for the 7.5-mg dose (approximately 12- 14 hours) than for the 15-mg dose (24 hours). These data show that ambulatory BP was a more sensitive tool in the assessment of the antihypertensive effects of moexipril; that prolonged 24-hour efficacy of this ACE inhibitor was predicted by its acute effects; and that the duration of antihypertensive activity of moexipril appears to he extended by higher dosing.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Clinical Pharmacology|
|State||Published - 1995|
ASJC Scopus subject areas
- Pharmacology (medical)
- Pharmacology, Toxicology and Pharmaceutics(all)