Modified plasma and abomasal disposition of albendazole in nematode-infected sheep.
The influence of gastrointestinal nematode infection on the kinetics of albendazole (ABZ) and its metabolites, albendazole sulphoxide (ABZSO) and sulphone (ABZSO2) in plasma and abomasal fluid was investigated in sheep. A micronised suspension of ABZ was administered intraruminally at 7.5 mg kg-1 to the following groups of sheep: (a) non-parasitised (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 obtained 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 ABZSO2 were recovered in the bloodstream. The active metabolite ABZSO was recovered in plasma between 0.5 and 48 (uninfected), 60 (H. contortus infected) or 72 h (naturally infected sheep) post-administration. The area under the plasma concentration vs time curve (AUC) values for ABZSO were higher in both artificially infected (64.0 micrograms h ml-1) and naturally infected (79.3 micrograms h ml-1) sheep as compared with non-infected animals (41.8 micrograms h ml-1). Peak plasma concentrations for ABZSO and ABZSO2 were higher in both artificially and naturally infected sheep than in non-parasitised animals. No changes in the half-lives and mean residence times for these metabolites were observed in infected sheep. ABZ and its metabolites were found in the abomasum between 0.5 and 48 (infected animals) or 72 h (uninfected) post-treatment. The availability (total AUCs) of ABZ and its metabolites in abomasal fluid 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 metabolites in the abomasum. Such a phenomenon correlates with: (a) the higher total AUC values obtained for ABZ metabolites in the bloodstream of the infected compared to the control sheep, (b) the lower concentration profiles of the ABZ parent drug and its metabolites found in the abomasal fluid of the infected animals.
Alvarez
L I
LI
Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro, Tandil, Argentina.
Sánchez
S F
SF
Lanusse
C E
CE
D000018:Abomasum / Q000378:metabolism*; D015766:Albendazole / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D000871:Anthelmintics / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D006188:Haemonchiasis / Q000097:blood / Q000378:metabolism / Q000662:veterinary*; D006207:Half-Life; D008297:Male; D012756:Sheep; D012757:Sheep Diseases / Q000097:blood / Q000378:metabolism*
D000871:Anthelmintics; C027187:albendazole sulfone; D015766:Albendazole; C027186:albendazole sulfoxide