Tramadol elimination

The mean elimination half-life is about 6 h. The O-demethylation of tramadol to Ml, the main analgesic effective metabolite, is catalyzed by cytochrome P450 (CYP) 2D6, whereas A-demeth-ylation to M2 is catalyzed by CYP2B6 and CYP3A4. The wide variability in the pharmacokinetic properties of tramadol can partly be ascribed to CYP polymorphism. O- and A-demethylation of tramadol as well as renal elimination are stereoselective.56... 

Approximately one-third of both dihydrocodeine and tramadol are eliminated by the kidneys. Manufacturer s data for tramadol suggest that in hepatic or renal impairment the increase in half-life should be relatively low as long as one of these organs is functioning normally [48]. 

O-monodesmethyltramadol, A, 0-didesmethyl tramadol and their conjugates, and A-monodesmethyltramadol. O-Monodes-methyltramadol is an active metabolite and has a greater analgesic activity than the parent drug. About 90% of an oral dose is excreted in the urine in 3 days, about 30% of the dose as unchanged drug, and the rest as metabolites. The remainder of the dose is eliminated in the faeces. ... 

An unpublished study by the manufacturers found that the maximum plasma levels and the elimination half-life of a single 50-mg dose of tramadol were reduced by 50% by carbamazepine 400 mg twice daily for 9 days. It is likely that carbamazepine increases the metabolism of tramadol. On the basis of this study the manufacturers say that the analgesic effectiveness of tramadol and its duration of action would be expected to be re-... 

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