Pharmacokinetic behavior in sheep and cattle of 5-chloro-2-(methylthio)-6-(1-naphthyloxy)-1H-benzimidazole, a new fasciolicide agent.
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.
Ramírez
N
N
Facultad de Farmacia, Universidad de Costa Rica, San José, Costa Rica.
Mayet
L
L
Del Rivero
L
L
Ibarra-Velarde
F
F
Castillo
R
R
Hernández-Campos
A
A
Jung-Cook
H
H
D000818:Animals; D000980:Antiplatyhelmintic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D002417:Cattle / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D005212:Fasciolidae / Q000187:drug effects; D005260:Female; D006207:Half-Life; D007093:Imidazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D010087:Oxides / Q000494:pharmacology; D012756:Sheep / Q000097:blood / Q000378:metabolism*; D013457:Sulfur Compounds / Q000494:pharmacology; D013458:Sulfur Dioxide / Q000494:pharmacology
C468032:5-chloro-2-methylthio-6-(1-naphthyloxy)-1H-benzimidazole; D000980:Antiplatyhelmintic Agents; D007093:Imidazoles; D009281:Naphthalenes; D010087:Oxides; D013457:Sulfur Compounds; D013458:Sulfur Dioxide; C405951:sulfur monoxide