Plasma disposition, faecal excretion and in vitro metabolism of oxibendazole following oral administration in horses.
Oxibendazole (OBZ) was administered to eight horses at an oral dose of 10 mg kg(-1) bodyweight each. Parent OBZ could only be detected in plasma at the 0.5 and 1.0 hours post administration sampling times and the mean maximum plasma concentration was 0.008 microg ml(-1). Parent OBZ was detected in faeces between 12 and 72 hours after administration and the highest dry faecal concentration was detected at 24 hours. An unidentified metabolite was detected in plasma between 0.5 and 72 hours. The unidentified metabolite in the plasma of treated horses corresponded to the second eluted metabolite in the in vitro study. Metabolism of OBZ to its metabolite in vitro was significantly inhibited by co-incubation with the cytochrome P450 inhibitor piperonyl butoxide. These results indicated that first-pass metabolism decreases OBZ bioavailability in horses. The in vitro metabolism of OBZ was significantly inhibited by piperonyl butoxide and this could be utilised to extend the exposure of nematodes to the parent molecule.
Gokbulut
C
C
Division of Veterinary Pharmacology, University of Glasgow, UK.
Nolan
A M
AM
McKellar
Q A
QA
D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D001682:Biological Availability; D001835:Body Weight; D002478:Cells, Cultured; D005243:Feces / Q000737:chemistry*; D022781:Hepatocytes / Q000378:metabolism; D006736:Horses; D013997:Time Factors
D000871:Anthelmintics; D001562:Benzimidazoles; C011321:oxibendazole