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  • Title: Pharmacokinetics of tramadol and the metabolite O-desmethyltramadol in dogs.
    Author: KuKanich B, Papich MG.
    Journal: J Vet Pharmacol Ther; 2004 Aug; 27(4):239-46. PubMed ID: 15305853.
    Abstract:
    Tramadol is an analgesic and antitussive agent that is metabolized to O-desmethyltramadol (M1), which is also active. Tramadol and M1 exert their mode of action through complex interactions between opiate, adrenergic, and serotonin receptors. The pharmacokinetics of tramadol and M1 were examined following intravenous and oral tramadol administration to six healthy dogs, as well as intravenous M1 to three healthy dogs. The calculated parameters for half-life, volume of distribution, and total body clearance were 0.80 +/- 0.12 h, 3.79 +/- 0.93 L/kg, and 54.63 +/- 8.19 mL/kg/min following 4.4 mg/kg tramadol HCl administered intravenously. The systemic availability was 65 +/- 38% and half-life 1.71 +/- 0.12 h following tramadol 11 mg/kg p.o. M1 had a half-life of 1.69 +/- 0.45 and 2.18 +/- 0.55 h following intravenous and oral administration of tramadol. Following intravenous M1 administration the half-life, volume of distribution, and clearance of M1 were 0.94 +/- 0.09 h, 2.80 +/- 0.15 L/kg, and 34.93 +/- 5.53 mL/kg/min respectively. Simulated oral dosing regimens at 5 mg/kg every 6 h and 2.5 mg/kg every 4 h predict tramadol and M1 plasma concentrations consistent with analgesia in humans; however, studies are needed to establish the safety and efficacy of these doses.
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