INFLUENCE OF FOOD ON THE INTRAVENOUS AND ORAL DOSE KINETICS OF PROPRANOLOL IN THE DOG

The intravenous and oral dose kinetics of propranolol were studied in the dog both in a fasted state and immediately after a meal consisting of 100 g of cooked beef liver. Fifty .mu.Ci of 3H-propranolol was administered intravenously simultaneously with a 40-mg oral dose of unlabeled propranolol. Plasma 3H-propranolol was measured by specific extraction and liquid scintillation spectrometry, and unlabeled plasma propranolol was determined by gas chromatography-mass spectrometry. Feeding significantly reduced (25%) the elimination half-life and increased (52%) the systemic clearance of intravenous propranolol. The increase in the systemic clearance of propranolol after feeding was mostly due to an increase (60%) in apparent hepatic blood flow, which appeared to remain elevated for 5-7 hr. The meal had no influence on the apparent volume of distribution or plasma binding. Feeding did not affect the area under the concentration-time curve of oral propranolol, but significantly delayed the rate of oral propranolol absorption, shifting the time to reach peak plasma levels from 60 to 158 min. The results of this study suggest that feeding alters the disposition of propranolol in the dog by producing a sustained increase in hepatic blood flow.