title: Evaluation of the use of Göttingen minipigs to predict food effects on the oral absorption of drugs in humans.
abstract: This study investigated the oral absorption of drugs in minipigs to predict food effects in man. The protocol was based on a previously described model in dogs and further investigated the food source (i.e., US FDA breakfast or a nutritional drink) and food quantities. Two poorly soluble compounds were investigated [pravastatin (negative food effect) and atazanavir (positive food effect)] in Göttingen minipigs after seven different food regimens. The gastric emptying rate was evaluated by coadministration of acetaminophen. In short, the results demonstrated longer gastric emptying times in minipigs when compared with humans, within a range from 2.3 to 8.4 h dependent on the food regimen. There were no significant differences in drug absorption between fed and fasted state for the two compounds. The study showed that the dog protocol could not be transferred directly to minipigs, but needs further investigation and adjustments in order to get a valid model using Göttingen minipigs for the evaluation of food effects on drug absorption in humans.
authors.affiliation: Department of Pharmacy, University of Copenhagen, Copenhagen, 2100, Denmark.
authors.forename: Martin Lau
authors.initials: ML
authors.lastname: Christiansen
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
authors.forename: Mats
authors.initials: M
authors.lastname: Garmer
authors.forename: Jakob
authors.initials: J
authors.lastname: Kristensen
authors.forename: Jette
authors.initials: J
authors.lastname: Jacobsen
authors.forename: Bertil
authors.initials: B
authors.lastname: Abrahamsson
authors.forename: Rene
authors.initials: R
authors.lastname: Holm
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017849:Animals, Inbred Strains; D001628:Beverages; D062408:Breakfast; D003718:Denmark; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002149:Energy Intake; D018565:Food-Drug Interactions; D005746:Gastric Emptying / Q000187:drug effects; D006801:Humans; D008297:Male; D023421:Models, Animal; D065568:Oral Mucosal Absorption; D012995:Solubility; D013045:Species Specificity; D013552:Swine; D013556:Swine, Miniature / Q000502:physiology*
chemical_list: D015507:Drugs, Investigational
keywords: bioavailability; food effects; food interaction; minipigs; pharmacokinetics; poorly soluble drugs