title: Pharmacokinetics of morphine after intramuscular injection in common goldfish Carassius auratus and Atlantic salmon Salmo salar.
abstract: Teleost fish have a nociceptive system and likely perceive pain. This warrants the development of analgesic protocols both for experimental surgery and for various husbandry procedures. Morphine is the standard analgesic against which the efficacy of other analgesics is assessed, and is the analgesic that has been most used in fish. The aims of this study were to describe the pharmacokinetics of morphine after an intramuscular (i.m.) injection in common goldfish and Atlantic salmon, and to illustrate the whole-body distribution of morphine in salmon following i.m. injection of tritiated morphine. In the kinetic experiment, goldfish and salmon were respectively i.m. injected with 40 and 100 mg morphine kg(-1) in the right dorsal epaxial musculature. Blood was drawn at predetermined time points. Plasma was analysed for morphine and metabolites using liquid chromatography-mass spectrometry (LC-MS/MS). Morphine had a Tmax (time at which the maximum plasma concentration was measured) of 0.5 h in both species. The Cmax (maximum plasma concentration) showed substantial inter-individual variation, with a mean (90% CI) of 187 (167 to 199) mg l(-1) in salmon and 37 (29 to 43) mg l(-1) in goldfish, as determined by bootstrap analysis. The mean elimination half-lives were 12.5 and 13.5 h in goldfish and in salmon, respectively. The degree of metabolism to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) was low, with levels of M3G exceeding those of M6G. The distribution study demonstrated that the levels of tritiated morphine in the anterior kidney surpassed those in the other organs. A substantial amount seemed to be excreted through the gastrointestinal tract, while little tritium activity could be detected in the central nervous system.
authors.affiliation: Department of Pharmacology and Toxicology, The Norwegian School of Veterinary Science, 0033 Oslo, Norway. janicke.nordgreen@veths.no
authors.forename: Janicke
authors.initials: J
authors.lastname: Nordgreen
authors.forename: Hanne Hustoft
authors.initials: HH
authors.lastname: Kolsrud
authors.forename: Birgit
authors.initials: B
authors.lastname: Ranheim
authors.forename: Tor Einar
authors.initials: TE
authors.lastname: Horsberg
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001345:Autoradiography; D002490:Central Nervous System / Q000000981:diagnostic imaging / Q000378:metabolism; D006054:Goldfish / Q000378:metabolism*; D006207:Half-Life; D007273:Injections, Intramuscular / Q000662:veterinary; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D009020:Morphine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011859:Radiography; D011877:Radionuclide Imaging; D020317:Salmo salar / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine