A short-term high fat diet increases exposure to midazolam and omeprazole in healthy subjects. (2nd July 2016)

• Record Type: Journal Article
• Authors: Achterbergh, Roos; Lammers, Laureen A.; van Nierop, Samuel; Klümpen, Heinz-Josef; Soeters, Maarten R.; Mathôt, Ron A. A.; Romijn, Johannes A.
• Is Part Of: Expert opinion on drug metabolism and toxicology. Volume 12:Number 7(2016:Jul.)
• Page Start: 715
• Page End: 720
• Publication Date: 2016-07-02
• Subjects: Cytochrome P450 -- drug metabolism and pharmacokinetics -- high fat diet -- nutrition; Drugs -- Toxicology -- Periodicals; Drugs -- Metabolism -- Periodicals; 615.7
• DOI: 10.1080/17425255.2016.1192126
• Languages: English
• ISSNs: 1742-5255

Abstract

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.