Comparative disposition of ricobendazole enantiomers after intravenous andsubcutaneous administration of a racemic formulation to calves

The enantioselective disposition kinetics of the benzimidazole anthelmintic , ricobendazole (RBZ), have been characterized after its intravenous (iv) a nd subcutaneous (sc) administration as a racemic formulation to cattle. The (+) and (-) RBZ enantiomeric forms were recovered in plasma after iv and s c administration of the racemic RBZ formulation, using a chiral phase based HPLC method. A biexponential plasma concentration versus time curve was ob served for both RBZ enantiomers following the iv treatment. Total body clea rance was higher for ( -) RBZ (150.4 m-L/h.kg) compared with that obtained for the ( +) RBZ antipode (78.1 mL/h.kg). The elimination half-life of the ( -) RBZ enantiomer was shorter (T1/2 beta: 2.67 h) compared with the (+) e nantiomer (T1/2 beta: 5.41 h). The plasma availability (expressed as AUC) w as significantly higher for (+) RBZ compared with that obtained for the (-) antipode following both treatments. The enantiomeric ratio in plasma at T- o was close to unity (50% of each enantiomer); the analysis of the concentr ation ratios (+) RBZ/(-) RBZ, demonstrated an increase in the proportion of ( +) RBZ during the time course of the kinetics after both iv and sc treat ments. The results presented herein show the enantioselective disposition k inetics of RBZ in cattle and are a further contribution to the understandin g of the kinetic behaviour of these sulphoxide-containing benzimidazole ant helmintics in ruminants. Copyright (C) 2000 John Wiley & Sons, Ltd.