title: Effects of age on the pharmacokinetics of tramadol and its active metabolite, O-desmethyltramadol following intravenous administration to foals.
abstract: BACKGROUND
  Tramadol is an analgesic agent used in man and a number of veterinary species. The pharmacokinetics and behavioural effects of tramadol and its active metabolite have been described in mature horses, but not in young foals.
  
  
  OBJECTIVE
  To characterise the pharmacokinetics, metabolism and some induced behavioural and physiological responses following i.v. tramadol administration in the same group of foals on 4 different occasions, from a few days after birth to age 43 days.
  
  
  METHODS
  Experimental.
  
  
  METHODS
  Tramadol was administered i.v. (3 mg/kg bwt) to a group of 8 foals on 4 separate occasions at ages 6–8, 13–15, 20–22 and 40–43 days. Blood samples were collected prior to administration and at multiple times until 48 h post administration. Blood samples were analysed for tramadol and metabolite concentrations and pharmacokinetics determined at each age. Behavioural and physiological effects were also assessed.
  
  
  RESULTS
  The average volume of distribution was 5.10, 4.63, 4.02 and 3.84 l/kg bwt and clearance 3.44, 3.08, 3.14 and 2.69 l/h/kg bwt when foals were aged 6–8, 13–15, 20–22 and 40–43 days, respectively. There was not a significant difference in the elimination half-life between age groups (1.52, 1.73, 1.13 and 1.51 for ages 6–8, 13–15, 20–22 and 40–43 days, respectively). The metabolites produced were the same as in mature horses; however, glucuronidation capability, appeared to increase with increasing age. Tramadol administration was well tolerated at all ages studied with sedation noted in the 3 older age groups.
  
  
  CONCLUSIONS
  Tramadol appears to be consistently well tolerated following i.v. administration of 3 mg/kg bwt to foals ranging in age from 1 to 6 weeks. Although analgesic concentrations in foals have yet to be established, the results of this study support further study of tramadol for clinical use in foals.
authors.forename: H K
authors.initials: HK
authors.lastname: Knych
authors.forename: E P
authors.initials: EP
authors.lastname: Steffey
authors.forename: A M
authors.initials: AM
authors.lastname: White
authors.forename: D S
authors.initials: DS
authors.lastname: McKemie
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D000831:Animals, Newborn; D019540:Area Under Curve; D005260:Female; D006207:Half-Life; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D008297:Male; D014147:Tramadol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D000701:Analgesics, Opioid; C080580:O-demethyltramadol; D014147:Tramadol; C080579:N-demethyltramadol