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

Abstract

The physicochemical properties, pK(a), Log P and solubility of compound alpha, (5-chloro-2-(methylthio)-6-(1-naphthyloxy)-1H-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 pK(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(1/2)) 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.

The Anti-Fasciolasis Properties of Silver Nanoparticles Produced by Trichoderma harzianum and Their Improvement of the Anti-Fasciolasis Drug Triclabendazole

“…These results are highly indicative of the presence of TCBZ-resistant Fasciola hepatica in sheep and cattle on this farm. The efficacy of the drug has been reported to be minimized due to drug resistance in animals [43,44]. The results of the present work showed that the drug efficacy on the hatchability of Fasciola eggs is increases drastically using silver nano particles combined with the drug of choice (10.33% and 30.33% respectively).…”

Ultrastructural changes to the tegumental system and the gastrodermal cells in adult Fasciola hepatica following in vivo treatment with the experimental fasciolicide, compound alpha

“…Thus, despite the strong plasma protein binding shown by TCBZ, experiments have shown that entry of this compound is predominantly across the tegument (Mottier et al 2006; Toner et al 2009). For compound alpha, it is most likely the sulphoxide and sulphone metabolites that penetrate the tegument, as they are present in the blood plasma of sheep, whereas compound alpha itself has not been detected (Rivero et al 1998; Ramírez et al 2008). In contrast to the results with compound alpha and TCBZ, disruption of the gastrodermal cells following treatment with the fasciolicides nitroxynil and clorsulon was consistently more severe than that of the tegument, pointing to oral uptake as the most important route of entry (McKinstry et al 2007; Meaney et al 2005 a , b , 2007).…”

“…While peak blood levels occur fairly quickly (10 h p.t. : Rivero et al 1998; Ramírez et al 2009), morphological changes take considerably longer to become apparent. They are not marked until 48 h p.t., becoming very severe by 72 h. This observation resembles the time-sequence observed with juvenile flukes (McConville et al 2008).…”

Surface changes in adult Fasciola hepatica following treatment in vivo with the experimental fasciolicide, compound alpha

“…The overall action of compound alpha appears to be relatively slow in relation to its pharmacokinetics, as the maximum blood levels of compound alpha sulphoxide are reached after only 14 h p.t. (Ramírez et al 2009). A similar timescale of action was observed for compound alpha against juvenile flukes .…”