MODIFIED PLASMA AND ABOMASAL DISPOSITION OF ALBENDAZOLE IN NEMATODE-INFECTED SHEEP

The influence of gastrointestinal nematode infection on the kinetics o f albendazole (ABZ) and its metabolites, albendazole sulphoxide (ABZSO ) and sulphone (ABZSO(2)) in plasma and abomasal fluid was investigate d in sheep. A micronised suspension of ABZ was administered intrarumin ally at 7.5 mg kg(-1) to the following groups of sheep: (a) non-parasi tised (control); (b) artificially infected with Haemonchus contortus; (c) naturally infected with Haemonchus contortus and other species of gastrointestinal nematodes. Plasma and abomasal fluid samples were obt ained serially over 72 h post-treatment and they were analysed by HPLC for ABZ and its metabolites. The ABZ parent drug was not detected in plasma at any time post-treatment, however the metabolites ABZSO and A BZSO(2) were recovered in the bloodstream, The active metabolite ABZSO was recovered in plasma between 0.5 and 48 (uninfected), 60 (H. conto rtus infected) or 72 h (naturally infected sheep) post-administration The area under the plasma concentration vs time curve (AUG) values for ABZSO were higher in both artificially infected (64.0 mu g h ml(-1)) and naturally infected (79.3 mu g h ml(-1)) sheep as compared with non -infected animals (41.8 mu g h ml(-1)). Peak plasma concentrations for ABZSO and ABZSO(2) were higher in both artificially and naturally inf ected sheep than in non-parasitised animals. No changes in the half-li ves and mean residence times for these metabolites were observed in in fected sheep. ABZ and its metabolites were found in the abomasum betwe en 0.5 and 48 (infected animals) or 72 h (uninfected) post-treatment. The availability (total AUCs) of ABZ and its metabolites in abomasal f luid were lower in H. contortus infected sheep than in the uninfected control animals, The increased abomasal pH induced by the presence of the H. contortus infection may reduce the plasma/abomasum pH gradient, which results in a decreased ionic-trapping of ABZ and its metabolite s in the abomasum, Such a phenomenon correlates with: (a) the higher t otal AUC values obtained for ABZ metabolites in the bloodstream of the infected compared to the control sheep, (b) the lower concentration p rofiles of the ABZ parent drug and its metabolites found in the abomas al fluid of the infected animals. (C) 1997 Elsevier Science B.V.