title: A short-term high fat diet increases exposure to midazolam and omeprazole in healthy subjects.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  A short-term hypercaloric high fat diet increases exposure to midazolam and omeprazole, possibly reflecting modulation of CYP3A4 and CYP2C19.
authors.affiliation: a Department of Internal Medicine, Academic Medical Center , University of Amsterdam , Amsterdam , The Netherlands.
authors.forename: Roos
authors.initials: R
authors.lastname: Achterbergh
authors.affiliation: b Hospital Pharmacy, Academic Medical Center , University of Amsterdam , Amsterdam , The Netherlands.
authors.forename: Laureen A
authors.initials: LA
authors.lastname: Lammers
authors.affiliation: c Department of Endocrinology and Metabolism, Academic Medical Center , University of Amsterdam , Amsterdam , The Netherlands.
authors.forename: Samuel
authors.initials: S
authors.lastname: van Nierop
authors.affiliation: d Department of Medical Oncology, Academic Medical Center , University of Amsterdam , Amsterdam , The Netherlands.
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Klümpen
authors.affiliation: c Department of Endocrinology and Metabolism, Academic Medical Center , University of Amsterdam , Amsterdam , The Netherlands.
authors.forename: Maarten R
authors.initials: MR
authors.lastname: Soeters
authors.affiliation: b Hospital Pharmacy, Academic Medical Center , University of Amsterdam , Amsterdam , The Netherlands.
authors.forename: Ron A A
authors.initials: RA
authors.lastname: Mathôt
authors.affiliation: a Department of Internal Medicine, Academic Medical Center , University of Amsterdam , Amsterdam , The Netherlands.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D059305:Diet, High-Fat; D006801:Humans; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009853:Omeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D003577:Cytochrome P-450 Enzyme System; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D009853:Omeprazole; D008874:Midazolam
keywords: Cytochrome P450; drug metabolism and pharmacokinetics; high fat diet; nutrition