Albendazole sulphoxide enantiomeric ratios in plasma and target tissues after intravenous administration of ricobendazole to cattle

The comparative concentration profiles of the (+) and (-) albendazole sulph oxide (ABZSO) enantiomers obtained in plasma and in selected target tissues /fluids after intravenous (i.v.) administration of a racemic formulation of ricobendazole (RBZ) to cattle were characterised. Fourteen Holstein calves received RBZ (racemic solution, 150 mg/mL) by i.v. administration at 7.5 m g/kg. Jugular blood samples were collected over 48 h post-treatment (plasma kinetic trial) and two animals were sacrificed at either 4, 12, 20, 28 or 32 h posttreatment to obtain samples of abomasal/small intestine mucosal ti ssue, abomasal/small intestine fluids, bile, liver and lung tissue (tissue distribution study). The (-)ABZSO enantiomer was depleted significantly fas ter from plasma compared with the (+)ABZSO antipode. The plasma AUC for (+) ABZSO (38.3 I-mug.h/mL) was significantly higher (P < 0.05) compared with t hat obtained for (-)ABZSO (20.5 <mu>g.h/mL). The (+)ABZSO enantiomer was th e predominant antipode measured in bile, abomasal fluid and abomasal mucosa . For instance, at 12 h post-treatment the (+)/(-) concentration ratios wer e: 12.9 (plasma), 1.62 (abomasal mucosa), 13.0 (abomasal fluid), 2.92 (inte stinal mucosa), 9.87 (intestinal fluid) and 21.5 (bile). No marked differen ces between the concentration profiles of both enantiomers were observed in the liver tissue. Albendazole (ABZ) was recovered from the liver, lung and gastrointestinal (GI) mucosal tissues of RBZ-treated calves up to 32 h pos t-treatment, probably produced by a GI microflora-mediated sulphoreduction of RBZ. An enantioselective kinetic behaviour may account both for the fast er depletion of the (-) enantiomer and for the higher availabilities of the (+) antipode observed in plasma and in most of the tissues/fluids investig ated. The simultaneous evaluation of the plasma kinetics and tissue concent ration profiles of both enantiomeric forms reported here, may help to inter pret the relationship between chiral behaviour and pharmacological action f or sulphoxide derivatives of benzimidazole (BZD) methylcarbamate anthelmint ics.