Tissue distribution of tramadol and metabolites in an overdose fatality

Tramadol (Ultram) is a centrally acting, synthetic analgesic agent. Althoug h it has some affinity for the opiate receptors, tramadol is believed to ex ert its analgesic effect by inhibiting the re-uptake of norepinephline and serotonin. There are several published cases of tramadol's involvement in d rug-related deaths and impairment. Reports of deaths involving tramadol alo ne with associated tissue concentrations are rare. This report documents a case in which tramadol overdose was identified as the cause of death. The f ollowing tramadol concentrations were found in various tissues: blood, 20 m g/L; urine, 110.2 mg/L; liver, 68.9 mg/kg; and kidney, 37.5 mg/kg. Tissue d istributions of the two primary metabolites, N-desmethyl and O-desmethyl tr amadol, are also reported. In each tissue or fluid except urine, the tramad ol concentration was greater than either metabolite consistent with other r eports of drug-impaired drivers and postmortem cases. The O-desmethyl metab olite concentration was greater than the N-desmethyl metabolite concentrati on in all tissues; this is in contrast to other postmortem reports, in whic h the majority of cases report concentrations of O-desmethyl as less than t hose of N-desmethyl. This may be useful as an indicator of time lapse betwe en ingestion and death.