| Item |
Information |
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Drug Groups
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approved; investigational |
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Description
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A narcotic analgesic proposed for moderate to severe pain. It may be habituating. [PubChem]
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| Indication |
Indicated in the treatment of moderate to severe pain. Consider for those prone to constipation or respiratory depression. Tramadol is used to treat postoperative, dental, cancer, and acute musculosketetal pain and as an adjuvant to NSAID therapy in patients with osteoarthritis. |
| Pharmacology |
Tramadol, a centrally-acting analgesic, exists as a racemic mixture of the trans isomer, with important differences in binding, activity, and metabolism associated with the two enantiomers. Although Tramadol is a synthetic analog of codeine, it has a significantly lower affinity for opioid receptors than codeine. |
| Toxicity |
LD50=350mg/kg (orally in mice) |
| Affected Organisms |
| • |
Humans and other mammals |
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| Biotransformation |
The major metabolic pathways appear to be N- and O- demethylation and glucuronidation or sulfation in the liver. One metabolite (O-desmethyltramadol, denoted M1) is pharmacologically active in animal models. |
| Absorption |
Racemic tramadol is rapidly and almost completely absorbed after oral administration. The mean absolute bioavailability of a 100 mg oral dose is approximately 75%.The mean peak plasma concentration of racemic tramadol and M1 occurs at two and three hours, respectively, after administration in healthy adults. |
| Half Life |
23 +/- 10 minutes |
| Protein Binding |
20% |
| Elimination |
Tramadol is eliminated primarily through metabolism by the liver and the metabolites are eliminated primarily by the kidneys. Tramadol and its metabolites are excreted primarily in the urine with observed plasma half-lives of 6.3 and 7.4 hours for tramadol and M1, respectively. Approximately 30% of the dose is excreted in the urine as unchanged drug, whereas 60% of the dose is excreted as metabolites. |
| Distribution |
* 2.6 L/kg [male 100 mg intravenous dose]
* 2.9 L/kg [female 100 mg intravenous dose] |
| Clearance |
* 5.9 mL/min/Kg [Healthy Adults, 100 mg qid, MD p.o]
* 8.5 mL/min/Kg [Healthy Adults, 100 mg SD p.o]
* 6.89 mL/min/Kg [Geriatric, (<75 yr), 50 mg SD p.o.]
* 4.23 mL/min/Kg [Hepatic Impaired, 50 mg SD p.o.]
* 4.23 mL/min/Kg [Renal Impaired, Clcr10-3mL/min, 100 mg SD i.v.]
* 3.73 mL/min/Kg [Renal Impaired, CLcr<5 mL/min, 100 mg SD i.v.]
* 6.4 mL/min/Kg [Male following a 100 mg IV dose]
* 5.7 mL/min/Kg [Female following a 100 mg IV dose] |
| References |
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Dayer P, Desmeules J, Collart L: [Pharmacology of tramadol] Drugs. 1997;53 Suppl 2:18-24.
[Pubmed]
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| • |
Harati Y, Gooch C, Swenson M, Edelman S, Greene D, Raskin P, Donofrio P, Cornblath D, Sachdeo R, Siu CO, Kamin M: Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy. Neurology. 1998 Jun;50(6):1842-6.
[Pubmed]
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| • |
Harati Y, Gooch C, Swenson M, Edelman SV, Greene D, Raskin P, Donofrio P, Cornblath D, Olson WH, Kamin M: Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy. J Diabetes Complications. 2000 Mar-Apr;14(2):65-70.
[Pubmed]
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| • |
Gobel H, Stadler T: [Treatment of post-herpes zoster pain with tramadol. Results of an open pilot study versus clomipramine with or without levomepromazine] Drugs. 1997;53 Suppl 2:34-9.
[Pubmed]
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Boureau F, Legallicier P, Kabir-Ahmadi M: Tramadol in post-herpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Pain. 2003 Jul;104(1-2):323-31.
[Pubmed]
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| External Links |
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