title: Pharmacokinetics of intravenous tramadol in dogs.
abstract: The purpose of this study was to determine the pharmacokinetics of tramadol and the active metabolite mono-O-desmethyltramadol (M1) in 6 healthy male mixed breed dogs following intravenous injection of tramadol at 3 different dose levels. Verification of the metabolism to the active metabolite M1, to which most of the analgesic activity of this agent is attributed to, was a primary goal. Quantification of the parent compound and the M1 metabolite was performed using gas chromatography. Pharmacodynamic evaluations were performed at the time of patient sampling and included assessment of sedation, and evaluation for depression of heart and respiratory rates. This study confirmed that while these dogs were able to produce the active M1 metabolite following intravenous administration of tramadol, the M1 concentrations were lower than previously reported in research beagles. Adverse effects were minimal, with mild dose-related sedation in all dogs and nausea in 1 dog. Analgesia was not documented with the method of assessment used in this study. Tramadol may be useful in canine patients, but additional studies in the canine population are required to more accurately determine the effective clinical use of the drug in dogs and quantification of M1 concentrations in a wider population of patients.
authors.affiliation: Small Animal Clinical Sciences, Veterinary Biomedical Sciences, Western College of Veterinary Medicine, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4.
authors.forename: Chantal J
authors.initials: CJ
authors.lastname: McMillan
authors.forename: Alex
authors.initials: A
authors.lastname: Livingston
authors.forename: Chris R
authors.initials: CR
authors.lastname: Clark
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Dowling
authors.forename: Susan M
authors.initials: SM
authors.lastname: Taylor
authors.forename: Tanya
authors.initials: T
authors.lastname: Duke
authors.forename: Rolf
authors.initials: R
authors.lastname: Terlinden
mesh_terms: D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D002849:Chromatography, Gas; D018592:Cross-Over Studies; D004285:Dogs / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D012119:Respiration / Q000187:drug effects; D014147:Tramadol / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000701:Analgesics, Opioid; C080580:O-demethyltramadol; D014147:Tramadol
references.citation: J Clin Pharm Ther. 2001 Aug;26(4):257-64
references.pmid: 11493367
references.citation: Anesth Analg. 1998 Aug;87(2):445-9
references.pmid: 9706948
references.citation: Drugs. 1994;47 Suppl 1:3-7
references.pmid: 7517823
references.citation: Am J Med. 1996 Jul 31;101(1A):47S-53S
references.pmid: 8764760
references.citation: Clin Pharmacol Ther. 1996 Dec;60(6):636-44
references.pmid: 8988065
references.citation: Drugs. 2000 Jul;60(1):139-76
references.pmid: 10929933
references.citation: Eur J Drug Metab Pharmacokinet. 2001 Jan-Jun;26(1-2):95-8
references.pmid: 11554441
references.citation: Eur J Pharmacol. 1992 Nov 24;224(1):83-8
references.pmid: 1360407
references.citation: J Pharmacol Exp Ther. 2003 May;305(2):710-8
references.pmid: 12606644
references.citation: Drug Metab Dispos. 1999 Nov;27(11):1293-9
references.pmid: 10534314
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2002 May 25;772(1):123-9
references.pmid: 12016023
references.citation: Clin Pharmacokinet. 2004;43(13):879-923
references.pmid: 15509185
references.citation: Anesth Analg. 2001 May;92(5):1319-21
references.pmid: 11323369
references.citation: Drug Metab Dispos. 1999 Oct;27(10):1133-42
references.pmid: 10497139
references.citation: J Vet Pharmacol Ther. 2004 Aug;27(4):239-46
references.pmid: 15305853
references.citation: Anesthesiology. 1999 Sep;91(3):639-47
references.pmid: 10485772
references.citation: J Pharmacol Exp Ther. 2000 Oct;295(1):352-9
references.pmid: 10992001
references.citation: J Cardiothorac Vasc Anesth. 2005 Aug;19(4):468-74
references.pmid: 16085251
references.citation: Vet Anaesth Analg. 2003 Oct;30(4):220-8
references.pmid: 12925179
references.citation: Xenobiotica. 2000 Jun;30(6):575-88
references.pmid: 10923860
references.citation: Drug Metab Dispos. 1998 Mar;26(3):278-83
references.pmid: 9492393
references.citation: Xenobiotica. 2001 Jul;31(7):423-41
references.pmid: 11531006
references.citation: J Chromatogr. 1986 Apr 25;377:213-20
references.pmid: 3711210
references.citation: Am J Health Syst Pharm. 1997 Mar 15;54(6):643-52
references.pmid: 9075493