RICOBENDAZOLE KINETICS AND AVAILABILITY FOLLOWING SUBCUTANEOUS ADMINISTRATION OF A NOVEL INJECTABLE FORMULATION TO CALVES

The plasma and abomasal fluid disposition kinetics of ricobendazole (R BZ) after subcutaneous (SC) administration of a novel injectable formu lation to calves, and the comparative plasma availability after sc inj ection of RBZ and that obtained after oral treatment with albendazole (ABZ), were characterised. Six parasite-free Holstein calves received RBZ (solution 150 mg ml(-1)) by sc injection at 3.75 mg kg(-1) (Experi ment 1). Experiment 2 was conducted in two experimental phases; in pha se I, five calves (Group A) received RBZ by SC injection and five anim als (Group B) were orally treated with ABZ (suspension 100 mg ml(-1)), at 5 mg kg(-1). Drug treatments were reversed for each group in phase II and given at 7.5 mg kg(-1). Samples of abomasal fluid (via cannula ) and jugular blood were collected over 72 hours post-treatment and an alysed by HPLC. RBZ and its sulphone metabolite were detected in plasm a following its SC administration. RBZ was rapidly absorbed, reaching the plasma C-max at 4.5 hours postdosing. The sulphone metabolite foll owed a similar kinetic pattern. Both molecules were rapidly and extens ively distributed into the abomasum, being detected in abomasal fluid between 30 minutes and 36 hours post-administration. An extensive plas ma/abomasum exchange process, with ionic-trapping in the abomasum, acc ounted for the higher AUC value (>200 per cent) obtained for RBZ in ab omasum compared with plasma. The sc treatment with RBZ formulated as a solution resulted in a significantly greater plasma availability (mea sured as ABZ sulphoxide) than the oral treatment with ABZ (suspension) given at the same dose rates.