Comparison of a chronotherapeutically administered beta blocker vs. a traditionally administered beta blocker in patients with hypertension.
Increasing systolic blood pressure and heart rate during the early morning results in increased myocardial oxygen demand. The use of beta blockers during this period may decrease cardiac workload, particularly in beta-blocker sensitive patients. The impact of a new chronotherapeutic beta blocker was assessed in 44 hypertensive patients. Patients were randomized to delayed-release propranolol (INP) dosed at 10 p.m. or to traditionally dosed propranolol (ILA) dosed at 8 a.m. for 4 weeks, following which they were switched to the alternative formulation for 4 weeks. Thirty-four-hour ambulatory blood pressure monitoring and pharmacokinetic measurements were obtained. INP and ILA resulted in significant reductions in mean 24-hour blood pressure (-9.0/-6.9 mm Hg and -10.4/-7.7 mm Hg, respectively). The top 25% of responders to high-dose propranolol (sensitive patients) were compared on each formulation. Mean trough reductions were -8.0/-6.7 mm Hg and -7.6/-5.8 mm Hg, respectively. Mean blood pressure reductions in the beta-blocker sensitive patients (n = 11) between 6 a.m. and noon were -15.2/-11.9 mm Hg on INP and -8.0/-4.6 mm Hg on ILA. Heart rate reduction was -14.1 bpm and double product reduction was -3319 in the INP patients between 6 a.m. and 12 noon compared with -10.5 and -2209 in the ILA patients. This study suggests that INP and ILA are effective once-a-day beta blockers, but the use of delayed-release propanolol results in a greater reduction in double product between 6 a.m. and noon in beta-blocker sensitive patients than does traditionally dosed propranolol.
Neutel
Joel M
JM
Orange County Research Center, Tustin, CA 92780, USA. jmneutel@aol.com
Rotenberg
Keith
K
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D020005:Propanols / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011433:Propranolol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D020005:Propanols; C477592:propranolol CR; D011433:Propranolol