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Pharmacokinetics of fenbendazole following intravenous and oral administration to pigs

Mads Bjelke Petersen DVM, PhD1,2 and Christian Friis DVM, PhD3
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  • 1 Department of Pharmacology and Pathobiology, Royal Veterinary and Agricultural University, 9 Ridebanevej, DK-1870 Frederiksberg C, Copenhagen, Denmark.
  • | 2 Present address is Scantox, 36A Hestehavevej, Ejby, DK-4623 Lille Skensved, Denmark.
  • | 3 Department of Pharmacology and Pathobiology, Royal Veterinary and Agricultural University, 9 Ridebanevej, DK-1870 Frederiksberg C, Copenhagen, Denmark.

Abstract

Objective—To determine pharmacokinetics and metabolic patterns of fenbendazole after IV and oral administration to pigs.

Animals—4 mixed-breed female pigs weighing 32 to 45 kg.

Procedure—Fenbendazole was administered IV at a dose of 1 mg/kg. One week later, it was administered orally at a dose of 5 mg/kg. Blood samples were collected for up to 72 hours after administration, and plasma concentrations of fenbendazole, oxfendazole, and fenbendazole sulfone were determined by use of high-pressure liquid chromatography. Plasma pharmacokinetics were determined by use of noncompartmental methods.

Results—Body clearance of fenbendazole after IV administration was 1.36 L/h/kg, volume of distribution at steady state was 3.35 L/kg, and mean residence time was 2.63 hours. After oral administration, peak plasma concentration of fenbendazole was 0.07 µg/ml, time to peak plasma concentration was 3.75 hours, and mean residence time was 15.15 hours. Bioavailability of fenbendazole was 27.1%. Oxfendazole was the major plasma metabolite, accounting for two-thirds of the total area under the plasma concentration versus time curve after IV and oral administration. Fenbendazole accounted for 8.4% of the total AUC after IV administration and 4.5% after oral administration.

Conclusions and Clinical Relevance—Results indicate that fenbendazole was rapidly eliminated from plasma of pigs. The drug was rapidly absorbed after oral administration, but systemic bioavailability was low. ( Am J Vet Res 2000;61:573–576)

Abstract

Objective—To determine pharmacokinetics and metabolic patterns of fenbendazole after IV and oral administration to pigs.

Animals—4 mixed-breed female pigs weighing 32 to 45 kg.

Procedure—Fenbendazole was administered IV at a dose of 1 mg/kg. One week later, it was administered orally at a dose of 5 mg/kg. Blood samples were collected for up to 72 hours after administration, and plasma concentrations of fenbendazole, oxfendazole, and fenbendazole sulfone were determined by use of high-pressure liquid chromatography. Plasma pharmacokinetics were determined by use of noncompartmental methods.

Results—Body clearance of fenbendazole after IV administration was 1.36 L/h/kg, volume of distribution at steady state was 3.35 L/kg, and mean residence time was 2.63 hours. After oral administration, peak plasma concentration of fenbendazole was 0.07 µg/ml, time to peak plasma concentration was 3.75 hours, and mean residence time was 15.15 hours. Bioavailability of fenbendazole was 27.1%. Oxfendazole was the major plasma metabolite, accounting for two-thirds of the total area under the plasma concentration versus time curve after IV and oral administration. Fenbendazole accounted for 8.4% of the total AUC after IV administration and 4.5% after oral administration.

Conclusions and Clinical Relevance—Results indicate that fenbendazole was rapidly eliminated from plasma of pigs. The drug was rapidly absorbed after oral administration, but systemic bioavailability was low. ( Am J Vet Res 2000;61:573–576)