INTERACTION OF PHENOBARBITAL WITH PROPRANOLOL IN THE DOG .3. BETA-BLOCKADE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 224  (1) , 62-67
Abstract
The chronic administration of phenobarbital (180 mg/day p.o. [orally]) alters the binding, bioavailability, metabolism and pharmacokinetics of propranolol. Phenobarbital affects the pharmacological activity of propranolol as measured by inhibition of isoproterenol tachycardia in dogs. Altered binding affects .beta.-blockade in 2 ways; a reduction in the free fraction and the volume of distribution. To separate the effects of active metabolites from the parent drug, an integrated form of the equation (DR - 1) = K.cntdot.(p) was used, where DR is the dose ratio and p is the concentration of the free (unbound) propranolol in plasma. The activity due to propranolol itself is subtracted from the total observed amount of .beta.-blockade. Phenobarbital increased the amount of .beta.-blockade which was due to active metabolites. Phenobarbital treatment shortened the time course of .beta.-blockade. The .beta.-blocking half-life for propranolol followed its pharmacokinetic half-life closely for a variety of experimental conditions. Pharmacological activity data could be used to describe pharmacokinetics without measuring blood concentrations.

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