Pharmacokinetics of tramadol, and its metabolite O-desmethyl-tramadol, in cats

Tramadol is an analgesic agent and is used in dogs and cats. Tramadol exerts its action through interactions with opioid, serotonin and adrenergic receptors. The opioid effect of tramadol is believed to be, at least in part, related to its metabolite, O-desmethyl-tramadol. The pharmacokinetics of tramadol and O-desmethyl-tramadol were examined after intravenous (i.v.) and oral administration of tramadol to six cats. A two-compartment model (with first-order absorption in the central compartment for the oral administration) with elimination from the central compartment best described the disposition of tramadol in cats. After i.v. administration, the apparent volume of distribution of the central compartment, the apparent volume of distribution at steady-state, the clearance, and the terminal half-life (mean +/- SEM) were 1553+/-118 mL/kg, 3103+/-132 mL/kg, 20.8+/-3.2 mL/min/kg, and 134+/-18 min, respectively. Systemic availability and terminal half-life after oral administration were 93+/-7% and 204+/-8 min, respectively. O-desmethyl-tramadol rapidly appeared in plasma following tramadol administration and had terminal half-lives of 261+/-28 and 289+/-19 min after i.v. and oral tramadol administration, respectively. The rate of formation of O-desmethyl-tramadol estimated from a model including both tramadol and O-desmethyl-tramadol was 0.014+/-0.003/min and 0.004+/-0.0008/min after i.v. and oral tramadol administration, respectively.