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        Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheep

        Author
        Sanchez, S.F.
        Jones, D. G.
        Small, J.
        McKellar, Quintin
        Attention
        2299/8508
        Abstract
        This study compared pharmacokinetic (PK) profiles in sheep dosed intravenously with three different concentrations of oxfendazole (OFZ). An in vitro plasma OFZ solubility study provided additional information on plasma saturation. For the PK study, 18 adult, parasite-free, female Suffolk cross sheep, allocated into three groups (n = 6), were treated intravenously, at a dose rate of 5 mg/kg bodyweight, with aqueous formulations containing at 4, 8 or 16% OFZ. Plasma drug concentrations were measured, for up to 72 h post-treatment, by a validated high performance liquid chromatography method with UV detection. OFZ and fenbendazole sulphone (FBZSO2) were the main metabolites detected in all three experimental groups. In animals given the 4% formulation, OFZ depleted according to a biexponential concentration vs. time curve. In contrast, those given 8 or 16% preparations produced atypical curves fitted by monoexponential equations. No statistically significant differences in area under concentration-time curves (AUC) were observed, but concentration-dependent differences in distribution and mean residence time (MRT) were evident. Compared with 4% OFZ, animals treated with 8 and 16% formulations had slower half-lives of metabolite formation, and lower AUC's, suggesting that OFZ sulphonation may have been modified. In vitro there was evidence of plasma saturation associated with 8 and 16% OFZ preparations. It is concluded that differences in PK profiles were related to OFZ solubility and/or tissue drug precipitation.
        Publication date
        2005
        Published in
        Journal of Veterinary Pharmacology and Therapeutics
        Published version
        https://doi.org/10.1111/j.1365-2885.2005.00678.x
        Other links
        http://hdl.handle.net/2299/8508
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