Tramadol pharmacokinetics

Pharmacokinetic properties Tramadol is extensively metabolized by O- and N-demethylation yielding the active metabolite O-desmethyl-tramadol (Ml) and several... 

Lee, C.R., McTavish, D., Sorkin, E.M. Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states, Drugs 1993, 46, 313-340. 

A purely hydrophilic matrix of hypromellose prolongs the release of tramadol from Tramal long (Fig. 3) developed by Gruenenthal. The tablets have the same dimensions, resulting in an identical release profile for all dosages (100, 150, 200 mg, see Fig. 4). For a titrated effect linear pharmacokinetics on increasing doses produce dose-proportional blood levels at any time. External influences, such as pH value, mechanical stress, surface-active... 

Members of the group of natural, semisynthetic, or synthetic alkaloid compounds prepared from opium are referred to as opioids. This group includes natural compounds usually denoted opiates, such as morphine and codeine, and the synthetic and semi synthetic compounds such as oxycodone, buprenorphine, fentanyl, methadone, and tramadol. The pharmacological effects and pharmacokinetic parameters of these drugs share many common characteristics and are illustrated with the prototypic drug in this class, morphine. 

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... 

Pharmacokinetic—pharmacodynamic characterization of tramadol is difficult because of differences between tramadol concentrations in plasma and at the site of action, and because of pharmacodynamic interactions between the two enantiomers of tramadol and its active metabolites.53... 

This chapter concentrates on some drug choices in acute rather than chronic pain, but the same principles can be used to determine the appropriateness of other types of analgesic. The drugs considered in this section are paracetamol, non-steroidal anti-inflammatories (NSAIDs specifically diclofenac, ibuprofen, indometacin, naproxen, sulindac and tenoxicam) and opioids (codeine, dihydrocodeine, morphine, pethidine and tramadol). Unless otherwise stated, all pharmacokinetic data originate from standard reference sources [1-5] and apply to adults only. 

There is a scarcity of information regarding use of codeine, dihydrocodeine and tramadol in patients with liver impairment. On the basis of pharmacokinetic properties, dihydrocodeine may be preferred over codeine. Owing to a lack of information and the potentially detrimental characteristics of tramadol, other opioids should be used in preference if possible. 

Tramadol Summary of Product Characteristics. Pliva. Electronic Medicines Compendium. Datapharm Communications Ltd. http //emc.medicines. org.uk/ (date accessed 2 March 2007 date of last text revision June 2003). Grond S, Sahlotzki A (2004) Clinical pharmacology of tramadol. Clin Pharmacokinet 43 879—923. 

Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet 2004 43 879-923. 

Campanero, M.A. Calahorra, B. Valle, M. Troconiz, I.F. Honorato, J. Enantiomeric separation of tramadol and its active metabolite in human plasma by chiral high-performance liquid chromatography application to pharmacokinetic studies. Chirality 1999, 11, 272-279. 

Data on file. Cited in Raffa RB, Nayak RK, Liao S, Minn FL. The mechanism(s) of action and pharmacokinetics of tramadol hydrochloride. Rev Contemp Pharmacother (1995) 6, 485-97. 

Parecoxib had no effect on the pharmacokinetics of alfentanil or fentanyl, and celecoxib and rofecoxib appeared not to affect the pharmacokinetics of tramadol Coxibs can reduce the perioperative opioid requirement, but adverse effects are not necessarily reduced. 

PunwaniNG. Tramadol pharmacokinetics and itspossible interactions with cyclooxygenase 2-selective nonsteroidal anti-inflammatory drugs. CUn Pharmacol Ther lQOA) 75,363-5. 

A placebo-controlled study in 12 healthy subjects found that quinidine 50 mg had virtually no effect on the analgesic effects of tramadol 100 mg but it inhibited its effect on pupil size. The manufacturers say that quinidine increases the tramadol AUC and maximum level by 25%, but this is within the normal pharmacokinetic variation seen with tramadol. Tramadol is partially metabolised to the active metabolite O-desmethyltramadol (which affects opioid receptors), by the cytochrome P450 isoenzyme CYP2D6, and it is this enzyme that is inhibited by quinidine. Blockade of the production of this metabolite appears to have little effect on the analgesic effect of tramadol. No special precautions seem to be needed. 

Barking RL. Extended-release tramadol (ULTRAM ER) a pharmacotherapeutic, pharmacokinetic, and pharmacodynamic focus on effectiveness and safety in patients with chronic/persistent pain. Am J Ther 2008 15 157-166. 

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