KINETICS OF DISTRIBUTION OF DL-PROPRANOLOL IN VARIOUS ORGANS AND DISCRETE BRAIN-AREAS OF THE RAT

  • 1 January 1980
    • journal article
    • research article
    • Vol. 214  (3) , 682-687
Abstract
The kinetics of distribution of dl-propranolol (P) to various organs and tissues were studied in the rat after an i.v. dose of 2 mg/kg. The disposition of the drug can be adequately described by a 2-compartment open model with a distribution half-life of 4.8 min, a terminal blood half-life of 63 min and an apparent volume of distribution .beta. of 8.5 l/kg. Higher tissue concentrations were present in heart, brain and kidney. Although the disappearance rate of P from abdominal aorta, muscles, adipose tissue and whole brain paralleled that of blood, the elimination rate constant for atria and kidney was significantly reduced suggesting a specific binding of P. After an i.v. dose of 5 mg/kg, P distributed rapidly to various brain areas following a vascularity pattern with higher concentrations in cortical areas of earlier times. An equilibrium between various brain areas was observed at 2-3 h after dosing. There was a parallel decay of P concentrations in the blood and in cortical areas, but the elimination constants were significantly reduced for hypothalamic nuclei and the medulla (C1 and C2), suggesting again a specific binding. Distribution, uptake and tissue binding of P in various peripheral organs and discrete brain areas is not a uniform process and this could explain discrepancies observed clinically between the pharmacodynamics and pharmacokinetics. There may be specific P binding sites in heart, kidney and brain which could be relevant to its mode of action.