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Pharmacokinetics of luxabendazole after oral and intravenous administration to sheep
A I Ortiz1, L Alvarez-Bujidos, I Ferre
1Departamento de Fisiología, Farmacología y Toxicología, Facultad de Veterinaria, Universidad de León, Spain.
Objective:
To determine pharmacokinetics of luxabendazole after oral and i.v. administration to healthy sheep.
Animals:
7 clinically normal female Merino sheep between 9 and 12 months old.
Procedure:
Pharmacokinetics were determined after oral and i.v. administration of luxabendazole at a dose of 10 mg/kg of body weight. Serial blood samples were collected for 56 hours after administration. Plasma concentrations of luxabendazole were determined by high-pressure liquid chromatography.
Results:
After i.v. administration, elimination of luxabendazole was slow, with a mean half-life of 8.72 hours. Mean steady-state volume of distribution and mean distribution volume during the elimination phase were 3.18 and 3.10 L/kg, respectively. Mean clearance was 0.24 L/kg.h, and mean area under the concentration-time curve was 41.89 mg.h/L. After oral administration, luxabendazole was slowly absorbed from the gastrointestinal tract. Mean absorption half-life was 2.26 hours. Peak plasma concentration was 0.50 microgram/ml and was detected 14 to 16 hours after drug administration. Mean area under the concentration-time curve was 12.03 mg.h/L. Mean bioavailability was 29%.
Conclusions:
Results suggest that luxabendazole is moderately absorbed from the gastrointestinal tract in sheep, is widely distributed into extravascular compartments, and is cleared slowly.
Clinical Relevance:
Determination of pharmacokinetic parameters is the first step in determining a safe and efficacious dosage regimen for luxabendazole in sheep.