A short-term high fat diet increases exposure to midazolam and omeprazole in healthy subjects |
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| Authors: | Roos Achterbergh Laureen A Lammers Samuel van Nierop Heinz-Josef Klümpen Maarten R Soeters Ron A A Mathôt |
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| Institution: | 1. Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlandsr.achterbergh@amc.uva.nl;3. Hospital Pharmacy, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;4. Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;5. Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands |
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| Abstract: | Objectives: Knowledge of factors contributing to variation in drug metabolism is of vital importance to optimize drug treatment. This study assesses the effects of a short-term hypercaloric high fat diet on metabolism of five oral drugs, which are each specific for a single P450 isoform: midazolam (CYP3A4), omeprazole (CYP2C19), metoprolol (CYP2D6), S-warfarin (CYP2C9) and caffeine (CYP1A2).Methods: In 9 healthy volunteers, pharmacokinetics of the five drugs were assessed after an overnight fast at two separate occasions: after a regular diet and after 3 days of a hypercaloric high fat diet (i.e. regular diet supplemented with 500 mL cream 1715 kcal, 35% fat]). Pharmacokinetic parameters (mean SEM]) were estimated by non-compartmental analysis.Results: The high fat diet increased exposure to midazolam by 19% from 24.7 (2.6) to 29.5 (3.6) ng ml-1h-1 (p=0.04) and exposure to omeprazole by 31% from 726 (104) to 951 (168) ng ml-1h-1 (p=0.05). Exposure to metoprolol, caffeine and S-warfarin was not affected by the high fat diet.Conclusion: A short-term hypercaloric high fat diet increases exposure to midazolam and omeprazole, possibly reflecting modulation of CYP3A4 and CYP2C19. |
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| Keywords: | Cytochrome P450 drug metabolism and pharmacokinetics high fat diet nutrition |
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