An in situ single-pass perfusion model for assessing absorption across the intestinal mucosa of the brushtail possum.
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.
McLeod
B J
BJ
AgResearch Invermay Agricultural Centre, PO Box 50034, Mosgiel, New Zealand. bernie.mcleod@agresearch.co.nz
Zhang
H
H
Huang
L
L
Thompson
E G
EG
Butt
A G
AG
Tucker
I G
IG
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*
D007987:Gonadotropin-Releasing Hormone; D019793:Fluorescein