Effects of age on the pharmacokinetics of tramadol and its active metabolite, O-desmethyltramadol following intravenous administration to foals

Heather K Knych, Eugene Steffey, A. M. White, D. S. McKemie

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Reasons for performing study: 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. Objectives: 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. Study design: 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.

Original languageEnglish (US)
Pages (from-to)65-71
Number of pages7
JournalEquine Veterinary Journal
Volume48
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Tramadol
intravenous injection
foals
Intravenous Administration
pharmacokinetics
Pharmacokinetics
metabolites
analgesics
Horses
Analgesics
Age Groups
O-demethyltramadol
horses
blood
sedation
Half-Life
physiological response
half life
Research Design
clinical trials

Keywords

  • Analgesia
  • Behaviour
  • Horse
  • Opioid
  • Pharmacokinetics
  • Tramadol

ASJC Scopus subject areas

  • Equine

Cite this

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title = "Effects of age on the pharmacokinetics of tramadol and its active metabolite, O-desmethyltramadol following intravenous administration to foals",
abstract = "Reasons for performing study: 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. Objectives: 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. Study design: 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.",
keywords = "Analgesia, Behaviour, Horse, Opioid, Pharmacokinetics, Tramadol",
author = "Knych, {Heather K} and Eugene Steffey and White, {A. M.} and McKemie, {D. S.}",
year = "2016",
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doi = "10.1111/evj.12364",
language = "English (US)",
volume = "48",
pages = "65--71",
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T1 - Effects of age on the pharmacokinetics of tramadol and its active metabolite, O-desmethyltramadol following intravenous administration to foals

AU - Knych, Heather K

AU - Steffey, Eugene

AU - White, A. M.

AU - McKemie, D. S.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Reasons for performing study: 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. Objectives: 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. Study design: 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.

AB - Reasons for performing study: 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. Objectives: 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. Study design: 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.

KW - Analgesia

KW - Behaviour

KW - Horse

KW - Opioid

KW - Pharmacokinetics

KW - Tramadol

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