title: Pharmacokinetics and physiologic effects of intramuscularly administered xylazine hydrochloride-ketamine hydrochloride-butorphanol tartrate alone or in combination with orally administered sodium salicylate on biomarkers of pain in Holstein calves following castration and dehorning.
abstract: OBJECTIVE
  To determine the pharmacokinetic parameters of xylazine, ketamine, and butorphanol (XKB) administered IM and sodium salicylate (SAL) administered PO to calves and to compare drug effects on biomarkers of pain and distress following sham and actual castration and dehorning.
  
  
  METHODS
  40 Holstein bull calves from 3 farms.
  
  
  METHODS
  Calves weighing 108 to 235 kg (n = 10 calves/group) received one of the following treatments prior to sham (period 1) and actual (period 2) castration and dehorning: saline (0.9% NaCl) solution IM (placebo); SAL administered PO through drinking water at concentrations from 2.5 to 5 mg/mL from 24 hours prior to period 1 to 48 hours after period 2; butorphanol (0.025 mg/kg), xylazine (0.05 mg/kg), and ketamine (0.1 mg/kg) coadministered IM immediately prior to both periods; and a combination of SAL and XKB (SAL+XKB). Plasma drug concentrations, average daily gain (ADG), chute exit velocity, serum cortisol concentrations, and electrodermal activity were evaluated.
  
  
  RESULTS
  ADG (days 0 to 13) was significantly greater in the SAL and SAL+XKB groups than in the other 2 groups. Calves receiving XKB had reduced chute exit velocity in both periods. Serum cortisol concentrations increased in all groups from period 1 to period 2. However, XKB attenuated the cortisol response for the first hour after castration and dehorning and oral SAL administration reduced the response from 1 to 6 hours. Administration of XKB decreased electrodermal activity scores in both periods.
  
  
  CONCLUSIONS
  SAL administered PO through drinking water decreased cortisol concentrations and reduced the decrease in ADG associated with castration and dehorning in calves.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Baldridge
authors.forename: Johann F
authors.initials: JF
authors.lastname: Coetzee
authors.forename: Steve S
authors.initials: SS
authors.lastname: Dritz
authors.forename: James B
authors.initials: JB
authors.lastname: Reinbold
authors.forename: Ronette
authors.initials: R
authors.lastname: Gehring
authors.forename: James
authors.initials: J
authors.lastname: Havel
authors.forename: Butch
authors.initials: B
authors.lastname: Kukanich
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000097:blood; D002077:Butorphanol / Q000008:administration & dosage / Q000097:blood; D002417:Cattle; D016231:Fluorescence Polarization Immunoassay; D005712:Galvanic Skin Response / Q000187:drug effects; D006733:Horns / Q000601:surgery*; D006854:Hydrocortisone / Q000097:blood / Q000493:pharmacokinetics; D007273:Injections, Intramuscular / Q000662:veterinary; D007649:Ketamine / Q000008:administration & dosage / Q000097:blood; D008297:Male; D009919:Orchiectomy / Q000662:veterinary*; D010149:Postoperative Pain / Q000188:drug therapy* / Q000662:veterinary*; D012980:Sodium Salicylate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D014991:Xylazine / Q000008:administration & dosage / Q000097:blood
chemical_list: D000700:Analgesics; D054316:Biomarkers, Pharmacological; D014991:Xylazine; D007649:Ketamine; D002077:Butorphanol; D006854:Hydrocortisone; D012980:Sodium Salicylate