title: Characterization of Pharmacokinetics in the Göttingen Minipig with Reference Human Drugs: An In Vitro and In Vivo Approach.
abstract: This study aims to expand our understanding of the mechanisms of drug absorption, distribution, metabolism and excretion in the Göttingen minipig to aid a knowledge-driven selection of the optimal species for preclinical pharmaceutical research.
  
  
  
  The pharmacokinetics of seven reference compounds (antipyrine, atenolol, cimetidine, diazepam, hydrochlorothiazide, midazolam and theophylline) was investigated after intravenous and oral dosing in minipigs. Supportive in vitro data were generated on hepatocellularity, metabolic clearance in hepatocytes, blood cell and plasma protein binding and metabolism routes.
  
  
  
  Systemic plasma clearance for the seven drugs ranged from low (1.1 ml/min/kg, theophylline) to close to liver blood flow (37.4 ml/min/kg, cimetidine). Volume of distribution in minipigs ranged from 0.7 L/kg for antipyrine to 3.2 L/kg for hydrochlorothiazide. A gender-related difference of in vivo metabolic clearance was observed for antipyrine. The hepatocellularity for minipig was determined as 124 Mcells/g liver, similar to the values reported for human. Based on these data a preliminary in vitro to in vivo correlation (IVIVC) for metabolic clearance measured in hepatocytes was investigated. Metabolite profiles of diazepam and midazolam compared well between minipig and human.
  
  
  
  The results of the present study support the use of in vitro metabolism data for the evaluation of minipig in preclinical research and safety testing.
authors.affiliation: Pharmaceutical Sciences, Roche Pharmaceutical Research and Early Development, F. Hoffmann - La Roche, Ltd, Basel, Switzerland. floriane.lignet@gmail.com.
authors.forename: Floriane
authors.identifier: 0000-0003-3262-6529
authors.initials: F
authors.lastname: Lignet
authors.affiliation: Pharmaceutical Sciences, Roche Pharmaceutical Research and Early Development, F. Hoffmann - La Roche, Ltd, Basel, Switzerland.
authors.forename: Eva
authors.initials: E
authors.lastname: Sherbetjian
authors.affiliation: Pharmaceutical Sciences, Roche Pharmaceutical Research and Early Development, F. Hoffmann - La Roche, Ltd, Basel, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Kratochwil
authors.affiliation: Pharmaceutical Sciences, Roche Pharmaceutical Research and Early Development, F. Hoffmann - La Roche, Ltd, Basel, Switzerland.
authors.forename: Russell
authors.initials: R
authors.lastname: Jones
authors.affiliation: Klinische Pharmakologie & Toxikologie, Universitätsspital Basel, Basel, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Suenderhauf
authors.affiliation: Pharmaceutical Sciences, Roche Pharmaceutical Research and Early Development, F. Hoffmann - La Roche, Ltd, Basel, Switzerland.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Otteneder
authors.affiliation: Pharmaceutical Sciences, Roche Pharmaceutical Research and Early Development, F. Hoffmann - La Roche, Ltd, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Singer
authors.affiliation: Pharmaceutical Sciences, Roche Pharmaceutical Research and Early Development, F. Hoffmann - La Roche, Ltd, Basel, Switzerland.
authors.forename: Neil
authors.initials: N
authors.lastname: Parrott
mesh_terms: D000818:Animals; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D023421:Models, Animal; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D013045:Species Specificity; D013552:Swine; D013556:Swine, Miniature
chemical_list: D004364:Pharmaceutical Preparations
keywords: in silico; metabolism; minipig; pharmacokinetics