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Increased clearance of propranolol and theophylline by high‐protein compared with high‐carbohydrate diet
Author(s) -
Fagan Timothy C,
Walle Thomas,
Oexmann Mary Joan,
Walle U Kristina,
Bai Stephen A,
Gaffney Thomas E
Publication year - 1987
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1987.48
Subject(s) - theophylline , propranolol , volume of distribution , pharmacokinetics , drug , chemistry , carbohydrate , plasma clearance , therapeutic index , endocrinology , oral administration , pharmacology , medicine , clinical pharmacology , clearance rate
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 plasma half‐life of 26% ± 6% (range 6% to 42%; P < 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. Clinical Pharmacology and Therapeutics (1987) 41 , 402–406; doi: 10.1038/clpt.1987.48