Pharmacokinetic behaviour of netobimin and its metabolites in sheep.
The pharmacokinetics and the profile of urine excretion of netobimin (NTB) and its metabolites were investigated after its intraruminal (i.r.) and subcutaneous (s.c.) administration to sheep at 20 mg/kg. Plasma and urine concentrations of NTB, albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2) were measured serially over a 120-h period by HPLC. NTB showed a similar pharmacokinetic profile in both treatments, being detected between 0.5 and 12 h post-treatment, but the tmax was achieved significantly earlier (P less than 0.05) after s.c. treatment. ABZ was detected in plasma only after i.r. treatment, resulting in a low area under the curve (AUC). The peak plasma concentration (Cmax) and AUC for ABZSO and ABZSO2 were significantly higher after i.r. administration of NTB. In both treatments, the ABZSO Cmax was reached earlier than the ABZSO2 Cmax. The ratio of AUC ABZSO2:ABZSO was higher following s.c. administration (1.33) than following i.r. administration (0.35). The percentages of total dose excreted in the urine as NTB, ABZ, ABZSO and ABZSO2 were 17.05 (i.r.) and 8.16 (s.c.). There was a less efficient conversion of NTB into ABZ metabolites after s.c. administration. The detection of ABZ in plasma and the high ABZSO AUC obtained after i.r. treatment may be of major importance for anthelmintic efficacy.
Lanusse
C E
CE
Institute of Parasitology, McGill University, Macdonald College, Quebec, Canada.
Prichard
R K
RK
D000042:Absorption; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D001711:Biotransformation; D006146:Guanidines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D007279:Injections, Subcutaneous / Q000662:veterinary; D008297:Male; D012417:Rumen / Q000378:metabolism; D012756:Sheep / Q000378:metabolism*
D000871:Anthelmintics; D006146:Guanidines; C049626:netobimin