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

• Published in: Journal of veterinary pharmacology and therapeutics 2009-04, Vol.32 (2), p.154-159
• Main Authors: RAMÍREZ, N, MAYET, L, DEL RIVERO, L, IBARRA-VELARDE, F, CASTILLO, R, HERNÁNDEZ-CAMPOS, A, JUNG-COOK, H
• Format: Article
• Language: English
• Subjects: Animals; antiparasitic agents; Antiplatyhelmintic Agents - blood; Antiplatyhelmintic Agents - pharmacokinetics; Antiplatyhelmintic Agents - pharmacology; benzimidazoles; bioavailability; biomarkers; blood chemistry; blood plasma; cattle; Cattle - blood; Cattle - metabolism; Chromatography, High Pressure Liquid - veterinary; compound alpha; dosage; drug evaluation; drug therapy; fascioliasis; Fasciolidae - drug effects; Female; Half-Life; hydrophobicity; Imidazoles - blood; Imidazoles - pharmacokinetics; Imidazoles - pharmacology; ionization; Male; Naphthalenes - blood; Naphthalenes - pharmacokinetics; Naphthalenes - pharmacology; new drugs; oral administration; Oxides - pharmacology; pharmacokinetics; sheep; Sheep - blood; Sheep - metabolism; solubility; species differences; Sulfur Compounds - pharmacology; Sulfur Dioxide - pharmacology; veterinary drugs
• ISSN: 0140-7783; 1365-2885
• DOI: 10.1111/j.1365-2885.2008.01014.x

The physicochemical properties, pKa, 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 pKa 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[fraction one₋half]) 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. Cmax 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.