Pharmacokinetics and pharmacodynamics of long-acting propranolol 60-mg capsules: a comparative evaluation.
This double-blind, placebo-controlled, four-period cross-over study was undertaken to evaluate the sustained-release characteristics of long-acting propranolol hydrochloride (Inderal LA, Ayerst Laboratories, New York, NY) 60 mg qd, to compare the pharmacokinetic and pharmacodynamic properties of this formulation with conventional propranolol 20 mg tid, and to evaluate the proportionality of long-acting propranolol 60 mg (LA 60 mg) and long-acting propranolol 80 mg (LA 80 mg). Pharmacodynamic effects were evaluated in 34 healthy subjects by assessing heart rate, systolic blood pressure, and the product of heart rate and systolic blood pressure (double product) after exercise-induced tachycardia following both acute (day 1) and steady state (day 4) drug administration. The Cmax following administration of LA 60 mg was 9.5 and 11.4 ng/mL on days 1 and 4, respectively, compared with 18.8 and 20.0 ng/mL with 20 mg tid (P less than .0001). The tmax for LA 60 mg was significantly later (P less than .0001) than for conventional propranolol. Additionally, the apparent plasma half-life was significantly longer (P less than .0001) than with conventional propranolol. The LA 60-mg formulation was dose proportional to the LA 80-mg formulation. Pharmacodynamic evaluations showed no significant differences between LA 60 mg and 20 mg tid at any times tested with either acute or steady state dosing. This study demonstrates that LA 60 mg displays characteristics of a sustained-release formulation, is proportional with LA 80 mg, and produces pharmacodynamic effects that are similar to 20-mg tid dosing.
Marino
M R
MR
Department of Clinical Research, Ayerst Laboratories, New York, New York.
Dey
M
M
Garg
D C
DC
Jallad
N S
NS
Dorick
D M
DM
Martinez
J J
JJ
Weidler
D J
DJ
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D005082:Physical Exertion; D011433:Propranolol / Q000097:blood / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D011433:Propranolol