Disposition kinetics of triclabendazole-sulpho metabolites in plasma and milk from orally treated dairy cows. Evaluation of drug residues in cheese

ORTIZ, P.; CABRERA, M.; IMPERIALE, F.; ALVAREZ, L.; PEREZ, J.; LANUSSE, C.

Lima

Congreso; XXII Congreso Panamericano de Ciencias Veterinarias; 2010

Asociacion Panamericana de Cs. Veterinarias

Triclabendazole (TCBZ) is a flukicidal halogenated benzimidazole compound. It is the drug of choice for treating liver fluke infections in livestock. At the present, in endemic areas as Cajamarca (Peru) where fasciolasis is recognized as a major problem in dairy cattle, parasite control strategies are implemented as regular antihelmintic treatments even during the lactating period. The milk obtained from treated dairy cattle does not have an adequate withdrawal time and it is commercialized as fresh milk, processed in dairy industries or consumed as fresh cheese. The current work was carried out to evaluate the disposition kinetics of TCBZ and its-sulpho metabolites, sulphoxide (TCBZSO) and sulphone (TCBZSO2) in plasma and milk, and to assess the presence of residual concentrations of TCBZ metabolites in cheese elaborated with milk obtained from treated dairy cows. Holstein dairy cows (n=7) were treated with TCBZ (Fasinex® 10%, Novartis) by oral route (12 mg/kg). Blood and milk samples were taken at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120 and 144 h post-treatment. The whole milk production of each treated animal was collected and used for cheese elaboration at 12, 24, 36, 48, 60 and 120 h post-treatment. The samples were analyzed using an HPLC-based methodology. Both sulpho-metabolites of TCBZ were detected in plasma and milk up to 144 h post-treatment. The TCBZSO and TCBZSO2 plasma concentrations reached the peak concentration of 26.8 µg/ml (TCBZSO) and 37.9 µg/ml (TCBZSO2) at 16 and 51 h post-treatment, respectively. The same metabolites were found in milk but the concentration levels were lower. The sulphone metabolite was the analyte recovered at the highest concentrations both plasma and milk. Consistently with the plasma kinetic results, TCBZSO2 was the metabolite excreted at the highest level in milk. The percentage of dose recovered in milk for TCBZSO2 was significantly higher (P < 0.001) than that obtained for TCBZSO. Residual concentrations of TCBZ-sulpho metabolites were found in cheese elaborated with milk from treated animals. The total average residual concentration in fresh cheese was 13.0-fold higher than that measured in the milk used for its elaboration. The strengthening of TCBZ-sulpho-metabolites concentration during the elaboration of fresh cheese should be seriously considered when using milk from treated cows.