NOCTURNAL DOSING OF A NOVEL DELIVERY SYSTEM OF VERAPAMIL FOR SYSTEMICHYPERTENSION

To evaluate the efficacy and safety of a novel delivery system of phys iologic patter release (PPR)-veropamil administered nocturnally to pat ients with stages I and II hypertension using ambulatory blood pressur e(BP) monitoring, we performed a multicenter (17 centers), double-blin d, randomized, placebo-controlled, parallel-group trial with placebo a nd 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 amb ulatory BP monitoring from 6 to 10 P.M. after 8 weeks of therapy, wher eas secondary measures included changes from baseline in peak, early m orning (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 statistic ally 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). Reduc tions in peak early morning (6 to 10 P.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 sys tem of verapamil administered nocturnally produced changes in BP that followed the circadian variability of BP: lower, but significant reduc tions during sleep, when ambulatory BP is intrinsically lowest in pati ents with hypertension, and appropriately larger reductions during ear ly morning awakening and daytime hours when ambulatory BP levels accel erate and plateau to the highest levels over a 24-hour period.