Effect of timing of administration on the plasma ACE inhibitory activity and the antihypertensive effect of quinapril

To assess whether timing of administration can influence the antihypertensive effect of quinapril, 18 patients with hypertension were studied with noninvasive ambulatory blood pressure monitoring. Quinapril, 20 mg, was given at 8 AM or 10 PM for 4 weeks in a double-blind crossover fashion. To study the pattern of angiotensin converting enzyme (ACE) inhibition with the two treatment regimens, plasma ACE activity was measured in seven subjects 2,4, 8, 12 and 24 hours after quinapril administration. The 24-hour blood pressure profiles showed a more sustained antihypertensive action with the evening administration of quinapril compared with the morning administration of quinapril; as with the morning administration, a partial loss of effectiveness was observed during nighttime hours. Measurement of ACE activity showed that evening administration caused a less pronounced but a more sustained decline of plasma ACE. These findings show that 20 mg quinapril given once daily is effective in lowering blood pressure levels throughout a 24-hour period. The evening administration seems to be preferable because it causes a more favorable modulation of ACE inhibition and therefore determines a more homogeneous 24-hour blood pressure control. Clinical Pharmacology and Therapeutics (1992) 52, 378–383; doi:10.1038/clpt.1992.158