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Abstract

1,8-Cineole (cineole) is a Eucalyptus leaf toxin that defends against predation by herbivores such as the
brushtail possum (Trichosurus vulpecula). The aim of the current study was to characterize the
pharmacokinetics of cineole in the possum to improve understanding about how possums can avoid
cineole toxicity when eating a Eucalyptus diet. Nine male possums were trapped in the wild and
acclimated to captivity; a subcutaneous port was then implanted for venous blood sampling. Cineole
was administered intravenously (10 and 15mgkg–1) via a lateral tail vein and orally (30, 100 and
300mg kg–1) by gavage, and blood concentrations of cineole and its metabolites were determined by
gas chromatography. Cineole had a large terminal volume of distribution (Vz¼27 l kg–1) and a high
clearance (43 ml min–1 kg–1), equal to hepatic blood flow. The terminal half-life was approximately 7 h.
Oral bioavailability was low (F¼0.05) after low doses, but increased tenfold with dose, probably due
to saturable first-pass metabolism. These findings indicate that when possums feed on a cineole diet,
they eat until the cineole consumed is sufficient to saturate pre-systemic metabolism, leading to a rapid
rise in bioavailability and cineole blood levels, and a cessation of the feeding bout. This is the first
report on the pharmacokinetics of a dietary toxin in a wild herbivore, and provides insights into the
interactions between the blood concentration of a plant secondary metabolite and the browsing
behaviour of a herbivore.

Item Type:	Article
Authors/Creators:	McLean, SR and Boyle, RR and Brandon, S and Davies, NW and Sorensen, J
Keywords:	1,8-Cineole, monoterpene pharmacokinetics, monoterpene metabolism, brushtail possum (Trichosurus vulpecula), herbivory
Journal or Publication Title:	Xenobiotica
Publisher:	Informa Healthcare
ISSN:	0049-8254
DOI / ID Number:	10.1080/00498250701570277
Item Statistics:	View statistics for this item

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