Administration time-dependent effects of nifedipine GITS on ambulatory blood pressure in patients with essential hypertension

Abstract

Several studies have shown that the circadian pattern of blood pressure (BP) remains unchanged after either morning or evening dosing of several CCB, including amlodipine, isradipine, verapamil, nitrendipine, and cilnidipine. A previous trial on a very small number of patients (n=10) concluded that the time of administration of 30 mg/d nifedipine gastrointestinal therapeutic system (GITS) has no impact on therapeutic efficacy [Clin Investig. 1994;72:864–869]. We investigated the antihypertensive efficacy and effects on the circadian BP pattern of nifedipine GITS in doses of 30 and 60 mg/d administered at different times according to the rest-activity cycle of each patient. We studied 80 previously untreated patients with grade 1–2 essential hypertension (36 men and 44 women), 52.1±10.7 years of age, randomly assigned to receive nifedipine GITS (30 mg/d) as a monotherapy for 8 weeks either upon awakening or at bedtime. Uncontrolled patients were titrated to receive 60 mg/d nifedipine GITS for another 8 weeks. BP was measured at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 hours before and after every 8 weeks of therapy. The BP reduction after 8 weeks of therapy with the lower dose of 30 mg/d was slightly but not significantly larger after bedtime dosing (10.3 and 6.5 mm Hg reduction in the 24-hour mean of systolic and diastolic BP after nifedipine GITS on awakening; 12.0 and 7.2 mm Hg after bedtime dosing). In non-responders to this low dose, the efficacy of 60 mg/d nifedipine GITS was markedly larger after bedtime dosing (16.0 and 9.3 mm Hg in systolic and diastolic BP, as compared to 8.4 and 4.0 mm Hg after morning dosing; P<0.03). Moreover, bedtime administration of nifedipine GITS reduced the incidence of edema by 91% and the total number of secondary effects by 74% as compared to morning dosing (P=0.02). Independently of the time of administration, a single daily dose of 30 mg/d of nifedipine GITS efficiently reduces BP for the whole 24 hours of the day. The added efficacy with 30 mg/d, the marked benefits with 60 mg/d, and the safety profile of bedtime administration of nifedipine GITS should be taken into account when prescribing this CCB in the treatment of essential hypertension.