CARDIOVASCULAR EFFECTS, PHARMACOKINETICS, AND CONVERTING-ENZYME INHIBITION OF ENALAPRIL AFTER MORNING VERSUS EVENING ADMINISTRATION

The cardiovascular effects and pharmacokinetics of once-daily enalapri l were studied after single-dose and subchronic treatment in eight pat ients with hypertension by use of ambulatory blood pressure monitoring . Enalapril, 10 mg, was given at either 7 Am or 7 Pm in a randomized c rossover design. In addition, inhibition of serum converting enzyme wa s studied. Subchronic treatment at 7 Am significantly reduced blood pr essure during the day but was less effective at night. Subchronic dosi ng at 7 Pm significantly further decreased nighttime blood pressure fo llowed by a slow increase during the day, with no effect on elevated a fternoon values. Peak concentrations of enalaprilat were found 3.5 hou rs (morning) and 5.6 hours (evening) after drug intake (p < 0.05), whe reas peak effects occurred 7.4 hours (morning) and 12 hours (evening) after drug administration. In conclusion, 24-hour blood pressure profi les in patients with hypertension were significantly influenced by the time of enalapril dosing. Differences in effect profiles could not be attributed to similar changes in pharmacokinetics or to different tim e courses of angiotensin converting enzyme inhibition.