Effect of Imidapril in Dipper and Nondipper Hypertensive Patients: Comparison Between Morning and Evening Administration

Abstract

The purpose of the study was to identify differences in the patterns of efficacy and duration of effects of imidapril administered at different times of the day (morning versus evening) in dipper and nondipper hypertensive patients. Twenty patients with untreated hypertension were classified into two groups: dippers (n = 9) and nondippers (n = 11). Imidapril (10 mg) was given at 07:00 or 18:00 for 4 weeks in a crossover fashion. Blood pressure (BP) and heart rate (HR) were monitored before and after morning and evening treatment every 30 min for 48h by ambulatory BP monitoring (ABPM). In dipper hypertension, the mean 48h BP was reduced with both doses. The decrease in the diurnal BP was stronger when the drug was administered in the evening than morning, but without significant difference. In nondipper hypertension, the systolic BP decreased at night with both doses, but the extent of the nocturnal reduction in systolic BP was greater after morning therapy. There were no significant differences in the decrease in BP during the day or night between the morning and evening administrations. When imidapril was administered in the morning, its serum concentration reached a maximum at 16:00, and when the drug was administered in the evening, it reached a maximum at 6:00. In dipper hypertension, the time taken for the blood concentration of imidapril to reach a maximum changed depending on its time of administration, and the time when the maximum antihypertensive effect of the drug appeared was different. In nondipper hypertension, decreases in the BP were confirmed at night regardless of the time of administration; this might be caused by angiotensin converting enzyme (ACE) inhibitors effectively blocking the BP from increasing by activating the parasympathetic nervous system. Therefore, when assessing the effectiveness of antihypertensive agents, factors such as the various patterns of BP before therapy and administration time must be considered.

Nocturnal hypertension: Will control of nighttime blood pressure prevent progression of diabetic renal disease?

“…Although this appears to be a predictable effect based on the duration of action of the two formulations, the effect was quite different in hypertensive non-dippers, in whom the antihypertensive effect of an 8:00 AM dose of shortacting diltiazem was most pronounced during nighttime rest [40]. This finding is not readily explained, and the effect of diltiazem-retard was not reported in non-dippers.…”

“…In hypertensive dippers, an 8:00 AM dose of diltiazemretard had the most marked antihypertensive effects during nighttime rest, whereas short-acting diltiazem given at the same time had the best effect during daytime activity [40]. Although this appears to be a predictable effect based on the duration of action of the two formulations, the effect was quite different in hypertensive non-dippers, in whom the antihypertensive effect of an 8:00 AM dose of shortacting diltiazem was most pronounced during nighttime rest [40].…”

Administration–time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension

“…Most, but not all, of these small sample-size investigations found greater effect of the evening schedule on the asleep than awake BP plus significant modification of the circadian BP profile towards a more normal dipping pattern. For example, Middeke et al [47] showed the combination of captopril and hydrochlorothiazide was slightly more effective in reducing night-time BP when administered in the evening, although Kohno et al [48] found no significant morning-evening, treatment-time difference in the control of the diurnal or nocturnal BP means with imidapril (10 mg/day) in their 20-patient crossover study.…”

Morning Versus Evening Administration of a Calcium Channel Blocker in Combination Therapy for Essential Hypertension by Ambulatory Blood Pressure Monitoring Analysis

“…[23][24][25][26][27][28][29][30][31][32] Greminger, et al studied the effect of morning versus evening administration of nifedipine gastrointestinal therapeutic system (GITS) in 15 patients with moderate hypertension and concluded that the time of administration of nifedipine GITS had no impact on daytime or nighttime BP control. 25) Mengden, et al reported that different timing of once-daily amlodipine administration does not influence its efficacy for 24-hour BP control.…”

“…For regimen 2, CCBs were administered separately at 4:00 pm, while other antihypertensive agents were given in the morning. After receiving regimen 1 antihypertensive treatment for 4 weeks, the patients underwent 24-hour ABPM to analyze their BP control. After the first ABPM, the patients were switched to regimen 2.…”