An in situ single-pass perfusion model for assessing absorption across the intestinal mucosa of the brushtail possum

Authors: Huang L, Tucker IG, Thompson EG, McLeod BJ, Butt AG, Zhang H
Publication: New Zealand Veterinary Journal, Volume 53, Issue 4, pp 234-241, Aug 2005
Publisher: Taylor and Francis

Animal type: Possum, Wildlife
Subject Terms: Abdomen, Alimentary system/gastroenterology, Animal remedies/veterinary medicines, Pharmacology, Physiology, Treatment/therapy
Article class: Scientific Article

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Abstract: AIM: 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) μg/ml in post-hepatic blood samples. When possums were perfused with 2.5 mg/ml fluorescein and 7 μg/ml LHRH (PE 2), mean plasma concentrations were 0.3 (SE 0.01) and 7.8 (SE 1.64) μg/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.
KEY WORDS: Brushtail possum, intestinal mucosa, fluorescein, LHRH, absorption, permeation enhancer

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