Comparative plasma disposition of fenbendazole, oxfendazole and albendazole in dogs.
The plasma disposition of fenbendazole (FBZ), oxfendazole (OFZ) and albendazole (ABZ); and the enantiospecific disposition of OFZ, and ABZSO produced were investigated following an oral administration (50 mg/kg) in dogs. Blood samples were collected from 1 to 120 h post-administration. The plasma samples were analysed by high performance liquid chromatography (HPLC). The plasma concentration of FBZ, OFZ, ABZ and their metabolites were significantly different from each other and depended on the drug administered. The sulphone metabolite (FBZSO2) of FBZ was not detected in any plasma samples and the parent molecule ABZ did not reach quantifiable concentrations following FBZ and ABZ administration, respectively. OFZ and its sulphone metabolite attained a significantly higher plasma concentration and remained much longer in plasma compared with FBZ and ABZ and their respective metabolites. The maximum plasma concentrations (Cmax), area under the concentration time curve (AUC) and mean residence time (MRT) of parent OFZ were more than 30, 68 and 2 times those of FBZ, respectively. The same parameters for ABZSO were also significantly greater than those of FBZSO. The ratio for total AUCs of both the parent drug and the metabolites were 1:42:7 for following FBZ, OFZ and ABZ administration, respectively. The enantiomers were never in racemic proportions and (+) enantiomers of both OFZ and ABZSO were predominant in plasma. The AUC of (+) enantiomers of OFZ and ABZSO was, respectively more than three and seven times larger than that of (-) enantiomers of both molecules. It is concluded that the plasma concentration of OFZ was substantially greater compared with FBZ and ABZ. The data on the pharmacokinetic profile of OFZ presented here may contribute to evaluate its potential as an anthelmintic drug for parasite control in dogs.
Gokbulut
C
C
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine and Research and Development Laboratory, University of Adnan Menderes, Aydin, Turkey. cengizgokbulut@yahoo.com
Bilgili
A
A
Hanedan
B
B
McKellar
Q A
QA
D000284:Administration, Oral; D015766:Albendazole / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004285:Dogs / Q000378:metabolism*; D005273:Fenbendazole / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D015203:Reproducibility of Results
D000871:Anthelmintics; D001562:Benzimidazoles; D005273:Fenbendazole; D015766:Albendazole; C011030:oxfendazole