Effect of Short-Term Fasting on Systemic Cytochrome P450-Mediated Drug Metabolism in Healthy Subjects: A Randomized, Controlled, Crossover Study Using a Cocktail Approach

Background and Objective Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance. Therefore, the aim of our study was to assess the effect of short-term fasting on oral bioavailability and systemic clearance of...

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Bibliographic Details
Published in:Clinical pharmacokinetics 2017-10, Vol.56 (10), p.1231-1244
Main Authors: Lammers, Laureen A., Achterbergh, Roos, van Schaik, Ron H. N., Romijn, Johannes A., Mathôt, Ron A. A.
Format: Article
Language:English
Subjects:
Alcohol
Bioavailability
Caffeine
Cancer therapies
Cell cycle
Chemotherapy
Cytochrome
Diet
Enzymes
Fasting
Internal Medicine
Liver
Medicine
Medicine & Public Health
Metabolism
Original
Original Research Article
Pharmacology/Toxicology
Pharmacotherapy
Population
Short term
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Summary:Background and Objective Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance. Therefore, the aim of our study was to assess the effect of short-term fasting on oral bioavailability and systemic clearance of different drugs. Methods In a randomized, controlled, crossover trial, 12 healthy subjects received a single administration of a cytochrome P450 (CYP) probe cocktail, consisting of caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A4), omeprazole (CYP2C19) and warfarin (CYP2C9), on four occasions: an oral (1) and intravenous (2) administration after an overnight fast (control) and an oral (3) and intravenous (4) administration after 36 h of fasting. Pharmacokinetic parameters of the probe drugs were analyzed using the nonlinear mixed-effects modeling software NONMEM. Results Short-term fasting increased systemic caffeine clearance by 17% ( p  = 0.04) and metoprolol clearance by 13% ( p  
ISSN:0312-5963
1179-1926
DOI:10.1007/s40262-017-0515-7