title: Pharmacokinetics of fentanyl following intravenous and transdermal administration in horses.
abstract: BACKGROUND
  Although fentanyl has been reported to cause CNS excitation in horses, a transdermal therapeutic system (TTS) containing this mu agonist has recently been used empirically in equine medicine to treat moderate to severe pain. A better understanding of the disposition of fentanyl following transdermal administration would facilitate the clinical use of TTS fentanyl to obtain analgesia in horses.
  
  
  OBJECTIVE
  To determine the pharmacokinetics of fentanyl following i.v. and TTS patch administration in healthy, mature horses and to evaluate the tolerance of horses to TTS fentanyl administration.
  
  
  METHODS
  The pharmacokinetics of fentanyl in serum were assessed following a single i.v. dose, a single TTS dose, and multiple TTS doses in 6 healthy horses. Physical examinations, haematology and serum biochemistry analyses during transdermal fentanyl application were then performed to determine tolerance of continuous fentanyl administration.
  
  
  RESULTS
  Fentanyl was very rapidly and completely absorbed following a single TTS dose. Mean serum fentanyl concentrations consistent with analgesia in other species were reached by 1 h and maintained until 32 h after patch application. Similar steady state serum concentrations were obtained when multiple doses of TTS fentanyl were administered every 48 or 72 h over 8 or 9 days, with less fluctuation in serum concentrations during the 48 h dosing interval. Three horses exhibited brief (< 12 h) episodes of increased body temperature; however, transdermal fentanyl administrations were not associated with other significant changes in haematology and biochemistry panels or physical examination findings.
  
  
  CONCLUSIONS
  Although the pharmacodynamics of fentanyl have not been investigated fully in horses, transdermally-administered fentanyl exhibited a favourable pharmacokinetic profile without clinically relevant side effects and may be a useful analgesic in equine patients.
authors.affiliation: K. L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, California 95616, USA.
authors.forename: L K
authors.initials: LK
authors.lastname: Maxwell
authors.forename: S M
authors.initials: SM
authors.lastname: Thomasy
authors.forename: N
authors.initials: N
authors.lastname: Slovis
authors.forename: C
authors.initials: C
authors.lastname: Kollias-Baker
mesh_terms: D000279:Administration, Cutaneous; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes / Q000662:veterinary; D004334:Drug Administration Schedule / Q000662:veterinary; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006736:Horses / Q000097:blood / Q000378:metabolism*; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000662:veterinary
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl