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Mechanisms and variations in the food effect on propranolol bioavailability
H Liedholm1, E Wåhlin-Boll, A Melander
1Department of Research in Primary Health Care, Lund University Health Sciences Centre, Dalby, Sweden.
European Journal of Clinical Pharmacology
|January 1, 1990
Summary
Eating a protein-rich meal significantly increases propranolol bioavailability in most individuals. This food effect, varying greatly between subjects, is linked to reduced liver drug processing, not enzyme inhibition.
Area of Science:
- Pharmacokinetics
- Drug Metabolism
- Gastrointestinal Physiology
Background:
- Food intake significantly influences drug absorption and bioavailability.
- Understanding food effects on propranolol is crucial for optimizing dosing strategies.
Purpose of the Study:
- To investigate the mechanisms and variability of food-induced changes in propranolol bioavailability.
- To differentiate the effects of protein-rich versus carbohydrate-rich meals.
Main Methods:
- Single-dose propranolol (80 mg) administration in healthy volunteers.
- Drug intake conditions: empty stomach, with protein-rich breakfast, with carbohydrate-rich/protein-poor breakfast.
- Analysis of propranolol and its oxidative metabolites (4-OHP, NLA, PG) in blood.
Main Results:
- Protein-rich meals increased propranolol bioavailability in most subjects, with significant inter-individual variation (decrease to 250% increase).
- Carbohydrate-rich, protein-poor meals did not significantly alter bioavailability.
- The food effect correlated with reduced oral clearance and was attributed to decreased hepatic extraction, likely due to increased hepatic entry rate.
Conclusions:
- Protein intake enhances propranolol bioavailability, primarily through reduced hepatic extraction rather than enzyme inhibition.
- Gastric absorption of propranolol may occur with protein-rich meals.
- Inter-individual variability in the food effect is linked to gastrointestinal absorption and hepatic blood flow rates.