Increased clearance of propranolol and theophylline by high-protein compared with high-carbohydrate diet

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Abstract
The objective of this study was to determine whether changes in dietary protein and carbohydrate influence the oral clearance of propranolol, a high-clearance drug, and theophylline, a low-clearance drug. Six normal subjects studied in a clinical research center each received a single oral dose of propranolol, 80 mg, and theophylline, 5 mg/kg, after having been on each of two well-defined diets for a period of 10 days. When the diet was altered from high carbohydrate/low protein to low carbohydrate/high protein, the oral clearance of propranolol increased by 74% .+-. 20% (mean .+-. SE; range 9% to 156%; P < 0.01) with no change in plasma half-life or plasma binding. This dietary change resulted in an increase in theophylline clearance of 32% .+-. 6% (range 18% to 50%; P < 0.02) and a corresponding decrease in palsma half-life of 26% .+-. 6% (range 6% to 42%; P < 0.05) with no alteration in the apparent volume of distribution. These observatons reemphasize the importance of diet in drug disposition and suggest that the clearance of high-clearance drugs like propranolol is more susceptible than the clearance of low-clearance drugs to dietary manipulations, effects that may have to be considered in drug therapy.