Increased clearance of propranolol and theophylline by high-protein compared with high-carbohydrate diet.
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 less than 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 less than 0.02) and a corresponding decrease in plasma half-life of 26% +/- 6% (range 6% to 42%; P less than 0.05) with no alteration in the apparent volume of distribution. These observations 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.
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004044:Dietary Proteins / Q000494:pharmacology*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007700:Kinetics; D008297:Male; D011433:Propranolol / Q000097:blood / Q000378:metabolism*; D013806:Theophylline / Q000097:blood / Q000378:metabolism*
D004040:Dietary Carbohydrates; D004044:Dietary Proteins; D011433:Propranolol; D013806:Theophylline