title: An in situ single-pass perfusion model for assessing absorption across the intestinal mucosa of the brushtail possum.
abstract: OBJECTIVE
  To develop an in situ animal model for assessing absorption of molecules across the intestinal mucosa of possums.
  
  
  METHODS
  A surgical preparation was used to perfuse known concentrations of reference compounds (fluorescein and luteinising hormone-releasing hormone; LHRH) through measured sections of selected regions (jejunum, caecum, proximal colon) of the intestinal tract of 19 possums, over a 2-h period. Plasma concentrations of the compounds, which were perfused either with or without co-administration of a permeation enhancer (sodium deoxycholic acid; SDA), were determined in the perfusion effluent, peripheral and in some instances in the pre-hepatic circulation by spectrofluorometry (fluorescein) or radioimmunoassay (LHRH). Pharmacokinetic parameters of both compounds in the possum were determined over a period of up to 4 h in a further 30 animals (fluorescein, n = 6; LHRH n = 24), from their plasma profiles following intravenous (I/V) administration of a bolus dose.
  
  
  RESULTS
  In animals perfused with 25 mg/ml fluorescein (Perfusion Experiment (PE) 1), the mean plasma concentration was 2.8 (SE 0.12) microg/ml in post-hepatic blood samples. When possums were perfused with 2.5 mg/ml fluorescein and 7 microg/ml LHRH (PE 2), mean plasma concentrations were 0.3 (SE 0.01) and 7.8 (SE 1.64) microg/ml fluorescein and 0.1 (SE 0.02) and 6.3 (SE 0.45) ng/ml LHRH, in the absence and presence of permeation enhancer, respectively. There was a poor correlation between pre-hepatic and post-hepatic concentrations.
  
  
  CONCLUSIONS
  The single-pass in situ perfusion technique provided a useful model for investigating basic information on the absorption of biocontrol agents across the intestinal tract of possums, but had limitations that must be recognised.
authors.affiliation: AgResearch Invermay Agricultural Centre, PO Box 50034, Mosgiel, New Zealand. bernie.mcleod@agresearch.co.nz
authors.forename: B J
authors.initials: BJ
authors.lastname: McLeod
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Huang
authors.forename: E G
authors.initials: EG
authors.lastname: Thompson
authors.forename: A G
authors.initials: AG
authors.lastname: Butt
authors.forename: I G
authors.initials: IG
authors.lastname: Tucker
mesh_terms: D000818:Animals; D019540:Area Under Curve; D019793:Fluorescein / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009893:Opossums / Q000378:metabolism*
chemical_list: D007987:Gonadotropin-Releasing Hormone; D019793:Fluorescein