CIVETAN   23983
CENTRO DE INVESTIGACION VETERINARIA DE TANDIL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Testing High Oxfendazole Doses to Treat Cysticercosis in Pigs: a Safety Assessment.
Autor/es:
ALVAREZ, L.; DOMINGUE, G.; MORENO, L.; CEBALLOS, L.; BISTOLETTI, M.; DONADEU, M.; LANUSSE, C.
Reunión:
Congreso; 12th International Congress of The European Association for Veterinary Pharmacology & Toxicology (EAVPT); 2012
Resumen:
Introduction: In addition to its well established nematodicidal activity, oxfendazole (OFZ) has shown good efficacy against the Taenia solium cyscticercus in pigs following its oral administration at 30 mg/kg (1). However, the use of this anthelmintic at such a high dose requires safety studies in target animals (pigs) before going ahead with the registration process. The goal of the current work was to assess the OFZ safety in pigs orally treated at 30 mg/kg. Complementary, the OFZ systemic exposure was measured. Materials and Methods: Thirty-two (32) healthy pigs (57 ± 6.9 kg) were used in the current study. The animals were divided into four experimental groups: OFZ30, OFZ90, OFZ150, which received OFZ (Synanthic® 9.06% oral suspension, Merial) at 30, 90 and 150 mg/kg, respectively, and an untreated Control Group. Treatments were performed by the oral route over three (3) consecutive days. Potential OFZ toxicity was assessed following VICH guidelines (2). Additionally, OFZ/metabolites plasma concentrations were quantified by HPLC at 3, 5 and 10 days after the first treatment. Parametric/non-parametric methods were used for the statistical comparison. Results: Mean body weights did not differ among the OFZ treated experimental groups throughout the study. Overall, the hematologic parameters for the experimental animals treated with OFZ at the different dose rates were within a normal range throughout the experiment. Normal values for all animals in the study were observed for serum glucose, total proteins, albumin and urea. The creatine kinase (CK) activity was above normal range in all animals. There were no significant changes in the urine parameters assayed. OFZ, fenbendazole and fenbendazole sulphone, were measured in plasma of the OFZ treated pigs.  The highest OFZ plasma concentration was measured at day 3 post-treatment and reached 8.9±2.8 (OFZ30), 15.0±2.9 (OFZ90) and 14.8±1.8 (OFZ150) µg/mL.   Conclusion: Only a temporary and partial reduction on food intake was observed in the pigs treated over 3 consecutive days with OFZ at 90 and 150 mg/kg. The observed increased serum CK activities seem to be originated in management-related stressful factors during the trial. Although the drug systemic availability (sum of OFZ plus metabolites AUC values) increased from 30 to 90 mg/kg, the systemic exposure remained similar for the treatment at 90 and 150 mg/kg. The overall evaluation of the collected data indicate that the 9.06% OFZ formulation administered orally to pigs at 30, 90 and 150 mg/kg daily for three consecutive days, did not significantly modify the health status of the treated pigs. Thus, it can be advised that OFZ treatment at 30 mg/kg can be a useful and safe recommendation to control cysticercosis in infected pigs.