title: Intestinal enzymatic metabolism of drugs.
abstract: OBJECTIVE
  The intestinal stability of perorally administered drugs has so far been determined using simulated intestinal fluid containing porcine pancreatin (SIF/P), as human gastrointestinal fluids are in most cases not available. In this study the metabolism of six low molecular mass drugs in SIF/P was compared with that in freshly collected porcine intestinal juice and on excised porcine intestinal mucosa.
  
  
  METHODS
  The drugs used were oseltamivir, atazanavir, diloxanide, diltiazem, cephalothin and cefoxitin. Metabolism studies were carried out by incubating each drug in the in-vitro models and by analysing the percentage of unmodified remaining drug at fixed time points.
  
  
  RESULTS
  Three drugs showed higher degradation on porcine mucosa compared with that in SIF/P and for five compounds a significantly higher metabolism in collected porcine intestinal juice versus SIF/P was observed. Metabolism of diloxanide furoate in collected intestinal juice, for example, was 40-fold higher compared with SIF/P. Moreover, the involvement of different metabolic pathways in porcine mucosa and intestinal juice was observed for cephalothin, being metabolized to desacetylcephalothin and thienyl-acetylglycine, whereas these metabolites were not found in SIF/P. In addition, diltiazem solution (0.25% m/v) was found to be significantly degraded in intestinal juice whereas its metabolism in SIF/P was negligible.
  
  
  CONCLUSIONS
  These findings demonstrated that the use of SIF/P for evaluation of presystemic drug metabolism could be highly misleading. Incubation of drugs in freshly collected porcine intestinal juice will likely lead to the improvement of the mimicry of body conditions to evaluate presystemic drug metabolism.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain, Josef Möller Haus, Innsbruck, Austria.
authors.forename: Federica
authors.initials: F
authors.lastname: Sarti
authors.forename: Jan
authors.initials: J
authors.lastname: Barthelmes
authors.forename: Javed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Fabian
authors.initials: F
authors.lastname: Hintzen
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000563:Amebicides / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D000998:Antiviral Agents / Q000378:metabolism*; D001826:Body Fluids / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004950:Esterases / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D010194:Pancreatin / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D013552:Swine; D013997:Time Factors
chemical_list: D000563:Amebicides; D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D002121:Calcium Channel Blockers; D010194:Pancreatin; D004950:Esterases; D010447:Peptide Hydrolases