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Pharmacokinetics of fentanyl administered transdermally and intravenously in sheep

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  • 1 Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348.
  • | 2 Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348.
  • | 3 Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348.
  • | 4 Pennsylvania Equine Toxicology & Research Center, West Chester University West Chester, PA 19382.
  • | 5 Pennsylvania Equine Toxicology & Research Center, West Chester University West Chester, PA 19382.
  • | 6 Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348.
  • | 7 Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348.

Abstract

Objective—To investigate the pharmacokinetics of fentanyl administered transdermally and IV in sheep.

Animals—21 adult female sheep.

Procedures—Fentanyl was administered IV to 6 healthy sheep. Transdermal fentanyl patches (TFPs) were applied to 15 sheep 12 hours prior to general anesthesia and surgery. Seria blood samples were collected for 18 hours after IV injection and 84 hours after TFP application. Fentanyl concentrations were quantified via liquid chromatography-mass spectrometry, and pharmacokinetic values were estimated.

Results—All sheep completed the study without complications. Following a dose of 2.5g/kg administered IV, the half-life was 3.08 hours (range, 2.20 to 3.36 hours), volume of distribution at steady state was 8.86 L/kg (range, 5.55 to 15.04 L/kg), and systemic clearance was 3.62 L/kg/h (range, 2.51 to 5.39 L/kg/h). The TFPs were applied at a mean dose of 2.05 g/kg/h. Time to maximum plasma concentration and maximal concentration were 12 hours (range, 4 to 24 hours) and 1.30 ng/mL (range, 0.62 to 2.73 ng/mL), respectively. Fentanyl concentrations were maintained at > 0.5 ng/mL for 40 hours after TFP application.

Conclusions and Clinical Relevance—IV administration of fentanyl resulted in a short half-life. Application of a TFP resulted in stable blood fentanyl concentrations in sheep. (Am J Vet Res 2010;71:1127—1132)

Abstract

Objective—To investigate the pharmacokinetics of fentanyl administered transdermally and IV in sheep.

Animals—21 adult female sheep.

Procedures—Fentanyl was administered IV to 6 healthy sheep. Transdermal fentanyl patches (TFPs) were applied to 15 sheep 12 hours prior to general anesthesia and surgery. Seria blood samples were collected for 18 hours after IV injection and 84 hours after TFP application. Fentanyl concentrations were quantified via liquid chromatography-mass spectrometry, and pharmacokinetic values were estimated.

Results—All sheep completed the study without complications. Following a dose of 2.5g/kg administered IV, the half-life was 3.08 hours (range, 2.20 to 3.36 hours), volume of distribution at steady state was 8.86 L/kg (range, 5.55 to 15.04 L/kg), and systemic clearance was 3.62 L/kg/h (range, 2.51 to 5.39 L/kg/h). The TFPs were applied at a mean dose of 2.05 g/kg/h. Time to maximum plasma concentration and maximal concentration were 12 hours (range, 4 to 24 hours) and 1.30 ng/mL (range, 0.62 to 2.73 ng/mL), respectively. Fentanyl concentrations were maintained at > 0.5 ng/mL for 40 hours after TFP application.

Conclusions and Clinical Relevance—IV administration of fentanyl resulted in a short half-life. Application of a TFP resulted in stable blood fentanyl concentrations in sheep. (Am J Vet Res 2010;71:1127—1132)

Contributor Notes

Address correspondence to Dr. Schaer (tpschaer@vet.upenn.edu).