In vivo and ex vivo uptake of albendazole and its sulphoxide metabolite bycestode parasites: relationship with their kinetic behaviour in sheep

The current experiments correlate the disposition kinetics of albendazole ( ABZ) following its intravenous (i.v.) and intraruminal (i.r.) administratio ns to Moniezia spp.-infected sheep, with the pattern of drug/metabolite upt ake by tapeworms collected from treated animals. The ex vivo uptake pattern of ABZ and albendazole sulphoxide (ABZSO) by the same cestode parasite was also investigated. Naturally infected (Moniezia spp.) Corriedale lambs wer e treated with ABZ by either i.v. (Group A, n=15) or i.r. (Group B, n=15) a dministration at 7.5 mg/kg. Plasma and abomasal fluid samples were obtained over a 120-h period. Two animals per group were killed at 0.5, 1, 2, 4 and 6 h post-treatment; parasite material (tapeworms), bile and intestinal flu id samples were recovered, Furthermore, Moniezia spp, tapeworms obtained fr om sheep killed at the local abattoir were incubated with either ABZ or ABZ SO for different time periods in a Kreb's Ringer Tris buffer (ex vivo exper iments). Samples were analysed by high performance liquid chromatography fo r ABZ, ABZSO and albendazole sulphone (ABZSO(2)). ABZ plasma concentrations decreased rapidly and were not detectable beyond 10 h following i.v. admin istration. ABZSO and ABZSO(2) were the metabolites recovered in plasma afte r both treatments. ABZ and its metabolites were extensively distributed to the digestive tract, mainly into the abomasal fluid, after the i.v. and i.r , administrations. The parent drug and its active ABZSO metabolite were rec overed in tapeworms collected from both i.v. and i.r. treated lambs. Howeve r, the availability of both ABZ and ABZSO was higher in parasite material r ecovered from i.v. treated animals. The uptake of ABZ by the cestode parasi te, both in vivo and ex vivo, was significantly greater than that of its su lphoxide metabolite, which agrees with the higher lipophilicity of the pare nt drug.