Chronopharmacology of Captopril plus Hydrochlorothiazide in Hypertension: Morning Versus Evening Dosing

Abstract

Blood pressure follows a strong circadian rhythm in normotensive people and in patients with primary hypertension. This may have several implications for antihypertensive therapy, including the time of dosing. For this reason we studied the influence of different dosing times on the antihypertensive effect over 24 h using ambulatory blood pressure monitoring (ABPM). We studied 13 male patients with moderate hypertension with controlled blood pressure over 12 months under a fixed combination of captopril and hydrochlorothiazide. The dosage of the combination therapy was then halved and given as one evening and then as one morning dose, each for 3 weeks. The combination therapy given twice daily showed a good 24-h antihypertensive effect after 12 months of treatment. During the following 6 weeks the mean 24-h blood pressure did not increase under half dosage, irrespective of whether under evening or morning dosing. However, mean daytime values (systolic and diastolic) of ABPM were significantly higher with evening dosing when compared both with full dosage and with half dosage given in the morning. The mean arterial blood pressure over 24 h showed the same differences as systolic and diastolic blood pressure, whereas heart rate was not significantly different between the three therapeutic regimens. ABPM seems to be an ideal method for chronopharmacological investigations under everyday conditions. Our study demonstrated significant differences in daytime blood pressure but not in 24-h blood pressure between morning and evening dosing of a fixed antihypertensive combination therapy.

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

“…When used in combination with other antihypertensive drugs, CCBs can exhibit a marked BP lowering effect and may induce a too potent hypotensive effect. [29][30] Third, too few ABPM measurements were obtained in this study; therefore, some data points with significant BP changes between these two regimens may have been missed.…”

“…[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.…”

Blutdruckvariabilität

“…Hier liegen prospektive Studiendaten vor, die sowohl das erhöhte Risiko bei Normabweichungen vom normalen Rhythmus zeigen, als auch für die individuelle Wahl des Dosierungszeitpunkts und der Dosierungsintervalle von Bedeutung sind [7,13,16,19,22]. Der saisonale Rhythmus mit höheren Werten im Winter [5] hat eine gewisse epidemiologische Bedeutung und ist am ehesten bedingt durch Kälte und Vitamin-D-Mangel.…”

“…die morgendliche gegen abendliche Einnahme in Cross-over-Studien [13]. Die erste Untersuchung bei Patienten mit primärer Hypertonie erfolgte 1991 [16]. [26].…”