Cardiovascular effects, pharmacokinetics, and converting enzyme inhibition of enalapril after morning versus evening administration

Abstract

The cardiovascular effects and pharmacokinetics of once-daily enalapril were studied after single-dose and subchronic treatment in eight patients with hypertension by use of ambulatory blood pressure monitoring. Enalapril, 10 mg, was given at either 7 AM or 7 PM in a randomized crossover design. In addition, inhibition of serum converting enzyme was studied. Subchronic treatment at 7 AM significantly reduced blood pressure during the day but was less effective at night. Subchronic dosing at 7 PM significantly further decreased nighttime blood pressure followed by a slow increase during the day, with no effect on elevated afternoon values. Peak concentrations of enalaprilat were found 3.5 hours (morning) and 5.6 hours (evening) after drug intake (p < 0.05), whereas peak effects occurred 7.4 hours (morning) and 12 hours (evening) after drug administration. In conclusion, 24-hour blood pressure profiles 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 time courses of angiotensin converting enzyme inhibition.

The importance of biological rhythms in drug treatment of hypertension and sex-dependent modifications

“…Several crossover studies (morning vs evening dosing) have been published for both ACE inhibitors 82,89,[126][127][128] and AT 1 -receptor blockers. [129][130][131] They demonstrated that in contrast to morning dosing, evening dosing of ACE inhibitors such as benazepril, enalapril, and perindopril resulted in a more pronounced nightly drop.…”

Trough to peak ratio as a guide to BP control: measurement and calculation

“…T:P ratio data achieved with morning administration may not apply to night-time dosing. 21,[40][41][42] T:P ratio may not represent the ideal guide to management of hypertensive patients. Rather it helps to determine whether BP is normalised during both day and night and whether the excessive acute rises seen in hypertensive individuals have been suppressed.…”

Ambulatory blood pressure profiles in essential hypertensives after treatment with a new once daily nifedipine formulation

“…However, previous studies using ABPM up to 48 hours including the second day of treatment showed for both the ␤-adrenoceptor-blocker atenolol 19 and the ACE-inhibitor enalapril 20 that though no significant BP reduction was observed after 20-24 hours after drug intake the effect reappeared the next day off therapy. Consequently, a reliable assess-ment of the duration of the antihypertensive effect cannot be provided by our study design with ABPM restricted to 24 hours.…”