Effect of timing of enalapril administration on 24-hour blood pressure control : morning versus evening

Abstract

Determines the effect of timing of enalapril administration (morning or evening) on the 24-hour blood pressure control by using 24-hour monitoring ambulatory blood pressure (ABP) in mild to moderate primary hypertensive patients in out-patients department at King Chulalongkorn Memorial Hospital. Twenty-five patients with seated diastolic blood pressure 90-110 mmHg and 24-hour mean ambulatory diastolic blood pressure > 85 mmHg after 2 weeks of placebo were allocated into the study. The dosage administered were 10 mg and 20 mg enalapril in mild (n = 15) and moderate (n = 10) hypertensive patients, respectively. They were randomly assigned to consume the drug either in the morning or in the evening time. After 4 weeks, the times for administering the drug were crossover. The office blood pressure and the ambulatory blood pressure were monitored at the end of each period. It was found that office BP, 24-hour BP and day-time BP were significantly reduced from baseline with either morning or evening administration with 10 mg or 20 mg per day dose of enalapril (p<0.01) but there were no statistically significant differences in the reduction of these BP between morning and evening administration, while the night-time BP was reduced by both regimens but the BP tended to be reduced to a greater extent with the evening administration as compared to the morning administration. Enalapril in the dose of 10 and 20 mg significantly reduced the early morning peak BP and the effect tended to be greater with the evening administration (p = 0.05-0.10). Trough:Peak ratios calculated for SBP and DBP were approximately 60% and 55% respectively with either morning or evening administration. The different time of administration did not effect the Trough:Peak ratios of the patients. Enalapril also induced significant reduction in BP loads during day-time and the whole 24-hour with either morning or evening administration (p<0.01), while night-time and peak morning BP loads were significantly reduced from baseline with evening administration (p<0.05) only. The antihypertensive effect was generated without the reflex tachycardia or other intolerance effects. Enalapril administered once daily either in the morning or in the evening could significantly reduce the blood pressure to nearly the same extent during day time. However, evening administration showed a more pronounced effect in the reduction of the blood pressure during nighttime and during peak morning time as compared to the effect caused by the morning administration. It is therefore depend on whether these pronounced effects are of benefit or risk to the individual patient in order to decide the best time of administration for each patient.