Nocturnal dosina of a novel delivery system of verapamil for systemic hypertension

To evaluate the efficacy and safety of a novel delivery system of physiologic pattern release (PPR)-verapamil administered nocturnaily to patients with stages I and II hypertension using ambulatory blood pressure (BP) monitoring, we performed a multicenter (17 centers), double-blind, randomized, placebo-controlled, parallel-group trial with placebo and 120, 180, 360, and 540 mg of verapamil in 287 randomized patients. The delivery system has a delay in the release of verapamil for 4 to 6 hours, and then delivers the drug from an osmotic pumping system for approximately 12 hours. Patients were dosed at 10 P.M. The primary end point was change from baseline in trough diastolic BP assessed by ambulatory BP monitoring from 6 to 10 P.M. after 8 weeks of therapy, whereas secondary measures included changes from baseline in peak, early morning (6 to 10 A.M.) systolic and diastolic BP, trough clinic BP, and 24-hour average daytime (8 A.M. to 8 P.M.) and nighttime (8 P.M. to 8 A.M.) BP. The 180, 360, and 540 mg verapamil doses achieved statistically significant reductions in trough (6 to 10 P.M.) diastolic BP (−3.9 ± 1.0, −7.8 ± 1.2, and −10.6 ± 1.1 mm Hg, respectively). Reductions in peak early morning (6 to 10 A.M.) diastolic BP were greater (−4.6 ± 0.9, −13.3 ± 1.2, and −19.0 ± 1.2, for 180, 360, and 540 mg, respectively). These data demonstrate that this novel delivery system of verapamil administered nocturnaily produced changes in BP that followed the circadian variability of BP: lower, but significant reductions during sleep, when ambulatory BP is intrinsically lowest in patients with hypertension, and appropriately larger reductions during early morning awakening and day-time hours when ambulatory BP levels accelerate and plateau to the highest levels over a 24-hour period.