Pharmacokinetics of tramadol and metabolites after injective administrations in dogs

The aim of this study was to determine the pharmacokinetics of tramadol and its main metabolites after IV and IM injections. The pharmacokinetic cross-over study was carried out on 6 healthy male beagle dogs. Tramadol was administered by intravenous (IV) and intramuscular (IM) injection at 4 mg/kg. Tramadol and its main metabolites O-desmethyl-tramadol (M1), N-,N-didesmethyl-tramadol (M2) and N-,O-didesmethyl-tramadol (M5) concentrations were measured in plasma samples by a HPLC coupled with fluorimetric detection; pharmacokinetic evaluations were carried out with a compartmental and non-compartmental model for tramadol and its metabolites, respectively. The bioavailability of the drug, ranging between 84-102% (mean 92%), was within the generally accepted values for a positive bioequivalence decision of (80-125%). After the IM injection the mean plasma drug concentration peak was reached after a Tmax of 0.34 h with a Cmax of 2.52 μg/mL. No therapeutic relevant differences were observed between IM and IV administration. The minimal effective plasma concentration was reached after a few minutes and maintained for about 6-7 h in both administrations. M1 plasma concentration was low and the amounts of the other metabolites produced were analogous in both routes of administration. In conclusion, tramadol was rapidly and almost completely absorbed after IM administration and its systemic availability was equivalent to the IV injection. The different onset time and duration of action observed were very small and probably therapeutically irrelevant. The IM injection is a useful alternative to IV injection in the dog.