Comparative efficacy of the (+) and (-) albendazole sulphoxide enantiomers against Haemonchus contortus

MOTTIER, L; CEBALLOS, L; ALVAREZ, L; LANUSSE, C

Philadelphia, Estados Unidos

Congreso; 49th American association of Veterinary Parasitologists(AAVP); 2004

Albendazole (ABZ), a broad spectrum benzimidazole anthelmintic widely used in human and veterinary medicine, is rapidly biotransformed into ABZ sulphoxide (ABZSO) and ABZ sulphone (ABZSO2). ABZSO is the main anthelmintically active molecule recovered in the bloodstream and tissues after ABZ administration to different animal species. ABZSO is a chiral molecule existing as the (+) and (-) enantiomeric forms. The (+)ABZSO predominates in plasma, tissues and target parasites obtained from ABZ-treated sheep. Previous work carried out in our lab permitted the characterization of the kinetic disposition of both enantiomers in parasite location tissues and in target parasites. However, the relative contribution of each enantiomeric form to the overall anthelmintic activity of ABZSO remains unknown. The work reported here evaluates the comparative anthelmintic activity of ABZ, racemic ABZSO (50% of each enantiomer), (+)ABZSO and (-)ABZSO against Haemonchus contortus using a jird (Meriones unguiculatus) model. ABZ susceptible H. contortus infective larvae (L3) were pre-incubated with 20 nmol/ml of either ABZ, racemic ABZSO, (+)ABZSO and (-)ABZSO or without drug (control) over  48 h. The purity of each incubated drug solution was confirmed by HPLC. After the incubation, the L3 were exsheated and orally administered to immunosuppressed jirds (1000 L3/jird, n=10). On day 13 postinfection, the jirds were killed, and the remaining parasites counted to determine the percentage of clearance (PC) for each molecule assayed (compared to the control group). The PC were: 99.3% (ABZ), 93.8% (racemic ABZSO), 93.8% (+ABZSO) and 72.5% (-ABZSO). These preliminary results indicate that the (+)ABZSO isoform has a significantly higher (P<0.05) nematodicidal activity than        (-)ABZSO, which confirms the pharmacological relevance of the higher concentrations of (+)ABZSO previously measured in tissues and target parasites collected from ABZ-treated animals.