Pharmacokinetic disposition of triclabendazole in cattle and sheep; discrimination of the order and the rate of the absorption process of its active metabolite triclabendazole sulfoxide

A comparative pharmacokinetic study was conducted to determine the order and the rate of absorption of triclabendazole (TCBZ) in cattle and sheep. A commercial suspension of TCBZ (Biofasiolex, Biogenesis S.A., Argentina) was administered at a dose rate of 10 mg/kg by the oral route to six Holstein f...

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Detalles Bibliográficos
Autores principales: Mestorino, Olga Nora, Formentini, E. A., Lucas, Mariana Florencia, Fernández, Cecilia, Modamio, P., Mariño Hernández, E., Errecalde, Jorge Oscar
Formato: Articulo
Lenguaje:Inglés
Publicado: 2008
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/135401
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Sumario:A comparative pharmacokinetic study was conducted to determine the order and the rate of absorption of triclabendazole (TCBZ) in cattle and sheep. A commercial suspension of TCBZ (Biofasiolex, Biogenesis S.A., Argentina) was administered at a dose rate of 10 mg/kg by the oral route to six Holstein female calves and six Corriedale female sheep. The plasma concentration profiles of the metabolites triclabendazole sulfoxide (TCBZ-SO) and triclabendazole sulfone (TCBZ-SO₂) were analysed by means of the non-compartmental method. The order of the absorption process of the active metabolite, TCBZ-SO, was determined by construction of curves of cumulative absorbed fraction of the drug by means of the Wagner-Nelson method. The appearance of TCBZ-SO in plasma of cattle and sheep resembles the entry of a constant quantity of drug into the organism per unit time. This is explained by the reservoir effect of the rumen, which acts as a biological slow-release system for TCBZ-SO and its precursor TCBZ to the posterior digestive tract where they are absorbed. The plasma concentration profiles of TCBZ-SO in both species were well described by a one-compartment open model with zero-order process of absorption and first-order process of elimination. The values of AUC<sub>0-∞</sub> and C<sub>max</sub> of TCBZ-SO did not differ between species, while other kinetic parameters except for λ<sub>z</sub> had higher values in calves than in sheep. In the case of TCBZ-SO₂, t<sub>max</sub> was the only parameter that did not differ between species, while other kinetic parameters except for λ<sub>z</sub> had higher values in calves than in sheep.