title: Novel delivery system for verapamil designed to achieve maximal blood pressure control during the early morning.
abstract: Because the risk of cardiovascular events appears to be greatest in the early morning, this period is a time during which adequate blood pressure (BP) control appears to be most desirable. In this study, a controlled-onset extended-release system (COER-24) that delivers verapamil in a manner designed to achieve maximal levels of drug during the early morning surge in BP was compared with placebo. Ninety-five patients with mild to moderate hypertension were studied. Of this group, 49 patients (mean age 57.6 +/- 1.4 years; 35 men and 14 women) were randomized to take verapamil COER-24 240 mg at 10 PM, and 46 subjects (mean age 55.8 +/- 1.5 years; 29 men and 17 women) were randomized to take placebo. Ambulatory BP monitoring was performed after a 4-week initial placebo period and was repeated after 4 weeks of treatment with verapamil or placebo. Verapamil COER-24 resulted in significant (p < 0.001) decreases in mean whole-day systolic and diastolic BP (-8.2/-6.3 mm Hg; baseline 152/93.0 mm Hg) when compared with placebo (+0.3/-0.9 mm Hg; baseline 150.3/93.2 mm Hg). From 6 AM to noon, verapamil COER-24 resulted in a change in systolic and diastolic BP of -11.6/-9.0 mm Hg, which was significantly (p < 0.001) greater than the change that occurred with placebo (-0.5/-1.0 mm Hg) during the same period. In the last 4 hours of the dosing interval (6 PM to 10 PM), verapamil COER-24 caused significantly greater (p < 0.001) decreases in BP (-7.4/-4.8 mm Hg) than did placebo (+2.7/+1.0 mm Hg). These data demonstrate that the COER-24 system, when administered in the late evening, achieves maximal BP reduction during the early morning hours. Moreover, BP reductions were sustained throughout the 24-hour period.
authors.affiliation: Orange County Heart Institute and Research Center, CA 92668, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Neutel
authors.forename: M
authors.initials: M
authors.lastname: Alderman
authors.forename: R J
authors.initials: RJ
authors.lastname: Anders
authors.forename: M A
authors.initials: MA
authors.lastname: Weber
mesh_terms: D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D014700:Verapamil / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D003692:Delayed-Action Preparations; D014700:Verapamil