title: Disposition, behavioural and physiological effects of escalating doses of intravenously administered fentanyl to young foals.
abstract: BACKGROUND
  Foal responses to a broader range of plasma fentanyl concentrations than currently reported are desirable to support (or not) clinical use.
  
  
  OBJECTIVE
  To describe fentanyl plasma concentrations following an escalating i.v. fentanyl dosing schedule in foals aged 5-13 days and describe selected, associated dose- and time-related behavioural and physiological responses to plasma fentanyl concentration.
  
  
  METHODS
  Experimental.
  
  
  METHODS
  Fentanyl was administered i.v. in an escalating fashion (2, 4, 8, 16 and 32 μg/kg bwt) at 10-min intervals. Blood samples were collected before and at selected times until 24 h post administration. Blood samples were analysed for fentanyl and metabolite concentrations and correlated with behavioural and physiological observations and selected blood analytes.
  
  
  RESULTS
  Foals mostly appeared to be unaffected following 2 μg/kg bwt (1.09 ± 0.41 μg/l; average maximal plasma concentration) of fentanyl, but 6 of the 8 foals appeared to be sedated following 4 μg/kg bwt (3.07 ± 1.11 μg/l). Ataxia with increased locomotor activity, muscle rigidity and head pressing posture was observed in many foals at 8 (7.24 ± 3.22 μg/l) and 16 μg/kg bwt (17.4 ± 5.67 μg/l). All foals were heavily sedated after 32 μg/kg bwt (34.5 ± 10.3 μg/l); 3 of the 8 foals became recumbent. The average (± s.d.) terminal half-life following administration of the final dose was 44.2 ± 9.85 min.
  
  
  CONCLUSIONS
  Behavioural and physiological responses to i.v. fentanyl in young foals are dose related. As with mature horses, the window of fentanyl plasma concentrations related to possible clinically desirable actions appears relatively narrow.
authors: K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, USA.|Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, USA.
authors: H K
authors: HK
authors: Knych
authors: K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, USA.|Department of Veterinary Surgery and Radiology, School of Veterinary Medicine, University of California, Davis, USA.
authors: E P
authors: EP
authors: Steffey
authors: K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, USA.
authors: H C
authors: HC
authors: Casbeer
authors: K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, USA.
authors: M M
authors: MM
authors: Mitchell
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D016292:Procedural Sedation / Q000662:veterinary*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006207:Half-Life; D006736:Horses; D007275:Injections, Intravenous; D008297:Male
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl
keywords: analgesic; fentanyl; foals; horse; opioid