After a single 100 mg dose peak plasma concentrations occur in approximately 2 hours. The plasma half life of tramadol and its active metabolite are 6 and 7 hours respectively. Tramadol steady state concentrations are achieved in two days based upon 4 times a day dosing. The only metabolite that is pharmacologically active is the M1 metabolite which is dependent on the cytochrome P450 CYP 2D6 isoenzyme. The most common adverse effects reported with tramadol use in phase IV trials involved the central nervous system and the gastrointestinal tract.
Seizures are a very serious side effect that have been reported with the use of tramadol.
Quinidine, a selective inhibitor of CYP 2D6 isoenzyme, results in increased concentrations of tramadol and reduced concentrations of the M1 metabolite. Cimetidine, a known enzyme inhibitor does not significantly alter the metabolism of tramadol. The recommended daily dose of tramadol may need to be doubled when individuals are taking the drug carbamazepine, an enzyme inducer, concomitantly with it. The expected symptoms of overdose are extensions of the pharmacologic effects and similar to other opioid agonists. The symptoms can include miosis, vomiting, coma, convulsions, and cardiovascular collapse.