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- Article] Pharmacokinetics of tramadol and its metabolites M1, M2 and M5 in horses following intravenous, immediate release (Fasted/Fed) and sustained release single dose administration
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DocNo of ILP: 4076
Doc. Type: Article
Title: Pharmacokinetics of tramadol and its metabolites M1, M2 and M5 in horses following intravenous, immediate release (Fasted/Fed) and sustained release single dose administration
Authors: Giorgi, M; Soldani, G; Manera, C; Ferrarini, P; Sgorbini, M; Saccomanni, G
Full Name of Authors: Giorgi, Mario; Soldani, Giulio; Manera, Clementina; Ferrarini, PierLuigi; Sgorbini, Micaela; Saccomanni, Giuseppe
Keywords by Author: tramadol; metabolism; horse; sustained-release; pharmacokinetic
Keywords Plus: MU-OPIOID RECEPTOR; LIVER-MICROSOMES; ANALGESIC DRUG; CLINICAL-TRIAL; PAIN; HYDROCHLORIDE; COMPONENTS; RATS
Abstract: Tramadol (T) is a centrally acting analgestic structurally related to codeine and morphine. This drug displays a weak affinity for the mu and delta-opioid receptors, and weaker affinity for the kappa-subtype; it also interferes with the neuronal release and reuptake of serotonin and nor-adrenaline in the descending inhibitory pathways. The metabolism of this drug has been investigated in different animals (rats, mice, Syrian hamsters, guinea pigs, rabbits, and dogs) and humans; similar metabolits are produced but in different amounts. The major metabolic pathways involved in phase I metabolite production (M1-M5) are O-demethylation, N-demethylation, and N,N-demethylation. The aim of the current study is to evaluate the pharmacokinetic profile of T in the horse, and its M1, M2, and M5 metabolites after single-dose administration (5 mg/kg body weight [BW]) by intravenous, sustained-release tablets and immediate-release capsules. We also will investigate the potential effects of fasting and feeding on bioavailability of immediate-release capsules. The study design was divided into four randomized phases. Twenty-four gelding Italian trotter race horses were divided into four groups (6 animals each) and administered T intravenously, with T immediate-release capsules in a fasting status, T sustained-release in fasting status. Blood samples were collected at different times and analyzed by high pressure liquid chromatography (HPLC) with fluorimetric detection. The limit of quantification was 5 ng/ml for T, M1, and M2, and 10 ng/ml for M5. A one-compartment model best fit the plasma concentrations of T and M2 after all treatments. Unfortunately, for M1 and M5, it was not always possible to fit plasma curves because of very low and variable concentrations. M2 was the main metabolite produced in the four different treatments and its concentration was higher than the concentration of T after sustained-release administration. Conversely, M1, the main metabolite in humans, and M5 seemed to be only marginally produced in the horse. When T was administered in both fasted and fed states, variations in some pharmacokinetic parameters were not considered clinically significant. We concluded that T could be administered in either a fasted or a fed condition.
Cate of OECD: Veterinary science
Year of Publication: 2007
Business Area: horse race
Detail Business: racehorse
Country: USA
Study Area:
Name of Journal: JOURNAL OF EQUINE VETERINARY SCIENCE
Language: English
Country of Authors: [Giorgi, Mario; Soldani, Giulio; Sgorbini, Micaela] Dept Vet Clin, I-56124 Pisa, Italy; [Manera, Clementina; Ferrarini, PierLuigi; Saccomanni, Giuseppe] Dept Pharmaceut Sci, I-56124 Pisa, Italy
Press Adress: Giorgi, M (reprint author), Dept Vet Clin, V le delle Piagge 2, I-56124 Pisa, Italy.
Email Address:
Citaion: Giorgi, Mario/0000-0003-3657-4703
Funding:
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Number of Citaion: 25
Publication: ELSEVIER SCIENCE INC
City of Publication: NEW YORK
Address of Publication: 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
ISSN: 0737-0806
29-Character Source Abbreviation: J EQUINE VET SCI
ISO Source Abbreviation: J. Equine Vet. Sci.
Volume: 27
Version: 11
Start of File: 481
End of File: 488
DOI: 10.1016/j.jevs.2007.10.004
Number of Pages: 8
Web of Science Category: Veterinary Sciences
Subject Category: Veterinary Sciences
Document Delivery Number: 246OY
Unique Article Identifier: WOS:000252017600005
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