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Abstract

Kinetics of distribution of di-propranolol in various organs and discrete brain areas of the rat.

G Bianchetti, J L Elghozi, R Gomeni, P Meyer and P L Morselli
Journal of Pharmacology and Experimental Therapeutics September 1980, 214 (3) 682-687;
G Bianchetti
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J L Elghozi
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R Gomeni
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P Meyer
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P L Morselli
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Abstract

The kinetics of distribution of di-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 two-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 liters/kg. Higher tissue concentrations were found to be 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 to 3 hr after dosing. There was a parallel decay of P concentrations in the blood and in cortical areas, whereas the elimination constants were significantly reduced for hypothealamic nuclei and the medulla (C1 and C2), suggesting again a specific binding. The data show that distribution, uptake and tissue binding of P in various peripheral organs and discrete brain areas is not a uniform process and they could give a partial explanation on the discrepancies observed clinically between the pharmacodynamics and pharmacokinetics. The data also suggest the possibility of specific P binding sites in heart, kidney and brain which could be of relevance for its mode of action.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 214, Issue 3
1 Sep 1980
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Abstract

Kinetics of distribution of di-propranolol in various organs and discrete brain areas of the rat.

G Bianchetti, J L Elghozi, R Gomeni, P Meyer and P L Morselli
Journal of Pharmacology and Experimental Therapeutics September 1, 1980, 214 (3) 682-687;

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Abstract

Kinetics of distribution of di-propranolol in various organs and discrete brain areas of the rat.

G Bianchetti, J L Elghozi, R Gomeni, P Meyer and P L Morselli
Journal of Pharmacology and Experimental Therapeutics September 1, 1980, 214 (3) 682-687;
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