Pharmacokinetic behavior in sheep and cattle of 5-chloro-2-(methylthio)-6-(1-naphthyloxy)-1 H-benzimidazole, a new fasciolicide agent.

The physicochemical properties, p K_a, Log P and solubility of compound alpha, (5-chloro-2-(methylthio)-6-(1-naphthyloxy)-1 H-benzimidazole), a new fasciolicide agent, were characterized using conventional methods. Also, its pharmacokinetics was evaluated in sheep and cattle. In both species an oral dose of 12 mg/kg was administered. Blood samples were collected during 144 h and analyzed by using an HPLC assay. Results showed that compound alpha is a weak base with a p K_a value of 2.87 and log P of 1.44. The solubility was very low in aqueous solvents. Pharmacokinetic studies showed that in both species compound alpha could not be detected at any sampling time. The mean half-life ( t_½) values of alpha sulphoxide in sheep and cattle were 19.86 and 29.87 h, while the half-life values of alpha sulphone were 19.43 and 46.32 h respectively. C_max values of alpha sulphoxide did not differ between species while alpha sulphone values were higher in cattle. Plasma protein binding of alpha sulphoxide was between 82% and 86%. These results, combined with the previous efficacy studies, suggest that compound alpha could be a promising fasciolicide agent. [ABSTRACT FROM AUTHOR]