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The mean elimination half-life is about 6 hours. Tramadol and its metabolites are mainly excreted via the kidneys. Tramadol is mainly metabolised by O- and N-demethylation and by conjugation reactions forming glucuronides and sulfates. Tramadol is rapidly distributed in the body plasma protein binding is about 20%. Sustained-release tablets release the active ingredient over a period of 12 hours, reach peak concentrations after 4.9 hours and have a bioavailability of 87–95% compared with capsules.
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After oral administration, tramadol is rapidly and almost completely absorbed. Tramadol is available as drops, capsules and sustained-release formulations for oral use, suppositories for rectal use and solution for intramuscular, intravenous and subcutaneous injection. The complementary and synergistic actions of the two enantiomers improve the analgesic efficacy and tolerability profile of the racemate. (+)-Tramadol inhibits serotonin reuptake and (−)-tramadol inhibits norepinephrine reuptake, enhancing inhibitory effects on pain transmission in the spinal cord. (+)-Tramadol and the metabolite (+)- O-desmethyl-tramadol (M1) are agonists of the μ.
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Tramadol, a centrally acting analgesic structurally related to codeine and morphine, consists of two enantiomers, both of which contribute to analgesic activity via different mechanisms.