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药品详细

Tramadol(曲马多)

化学结构式图
中文名
曲马多
英文名
Tramadol
分子式
C16H25NO2
化学名
(1R,2R)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexan-1-ol
分子量
Average: 263.3752
Monoisotopic: 263.188529049
CAS号
27203-92-5
ATC分类
N02A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

A narcotic analgesic proposed for moderate to severe pain. It may be habituating. [PubChem]

生产厂家
  • Actavis elizabeth llc
  • Alphapharm party ltd
  • Amneal pharmaceuticals llc
  • Apotex inc
  • Asta medica inc
  • Biovail laboratories international srl
  • Caraco pharmaceutical laboratories ltd
  • Cipher pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mallinckrodt inc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Northstar healthcare holdings ltd
  • Ortho mcneil janssen pharmaceuticals inc
  • Par pharmaceutical
  • Pliva inc
  • Purdue pharma products lp
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Victory pharma inc
  • Watson laboratories
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Dayer P, Desmeules J, Collart L: [Pharmacology of tramadol] Drugs. 1997;53 Suppl 2:18-24. Pubmed
  2. 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
  3. 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
  4. 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
  5. 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
剂型
规格
化合物类型
Type small molecule
Classes
  • Phenylpropylamines
Substructures
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Aromatic compounds
  • Anisoles
  • Phenylpropylamines
  • Phenyl Esters
适应症
药理
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.
Pharmacodynamics 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.
Mechanism of action Tramadol and its O-desmethyl metabolite (M1) are selective, weak OP3-receptor agonists. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. The analgesic properties of Tramadol can be attributed to norepinephrine and serotonin reuptake blockade in the CNS, which inhibits pain transmission in the spinal cord. The (+) enantiomer has higher affinity for the OP3 receptor and preferentially inhibits serotonin uptake and enhances serotonin release. The (-) enantiomer preferentially inhibits norepinephrine reuptake by stimulating alpha(2)-adrenergic receptors.
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.
Volume of distribution
  • 2.6 L/kg [male 100 mg intravenous dose]
  • 2.9 L/kg [female 100 mg intravenous dose]
Protein binding 20%
Metabolism
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.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Tramadol
O-Desmethyltramadol Details
Tramadol
N-Desmethyltramadol Details
Tramadol
    		N,N-didesmethyltramadol Details
    Tramadol
      		N,N,O-tridesmethyl-tramadol Details
      Tramadol
        		N,O-didesmethyltramadol Details
        Tramadol
          		O-Desmethyl-tramado glucuronide Details
          Route of 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.
          Half life 23 +/- 10 minutes
          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]
          Toxicity LD50=350mg/kg (orally in mice)
          Affected organisms
          • Humans and other mammals
          Pathways Not Available
          理化性质
          Properties
          State solid
          Experimental Properties
          Property Value Source
          melting point 180-181 °C Not Available
          water solubility Soluble in water. Not Available
          logP 2.4 Not Available
          pKa 9.41 Not Available
          Predicted Properties
          Property Value Source
          water solubility 7.50e-01 g/l ALOGPS
          logP 2.71 ALOGPS
          logP 2.45 ChemAxon
          logS -2.5 ALOGPS
          pKa (strongest acidic) 13.8 ChemAxon
          pKa (strongest basic) 9.23 ChemAxon
          physiological charge 1 ChemAxon
          hydrogen acceptor count 3 ChemAxon
          hydrogen donor count 1 ChemAxon
          polar surface area 32.7 ChemAxon
          rotatable bond count 4 ChemAxon
          refractivity 78.27 ChemAxon
          polarizability 30.45 ChemAxon
          药物相互作用
          Drug Interaction
          Almotriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Alvimopan Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
          Aminoglutethimide Aminoglutethimide may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
          Amiodarone Amiodarone may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Amiodarone may decrease the effect of Tramadol by decreasing active metabolite production.
          Amitriptyline Tramadol increases the risk of serotonin syndrome and seizures.
          Amoxapine Tramadol increases the risk of serotonin syndrome and seizures.
          Amprenavir Amprenavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Aprepitant Aprepitant may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Atazanavir Atazanavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Benzphetamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Bosentan Bosentan may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
          Bromocriptine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Cabergoline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Carbamazepine Carbamazepine may decrease the effect of tramadol by increasing Tramadol metabolism and clearance.
          Chloroquine Chloroquine may decrease the effect of Tramadol by decreasing active metabolite production.
          Chlorpromazine Chlorpromazine may decrease the effect of Tramadol by decreasing active metabolite production.
          Cimetidine Cimetidine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Cimetidine may decrease the effect of Tramadol by decreasing active metabolite production.
          Cinacalcet Cinacalcet may decrease the effect of Tramadol by decreasing active metabolite production.
          Citalopram The use of two serotonin modulators, such as citalopram and tramadol, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
          Clarithromycin Clarithromycin may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Clomipramine Tramadol increases the risk of serotonin syndrome and seizures. Clomipramine may decrease the effect of Tramadol by decreasing active metabolite production.
          Clotrimazole Clotrimazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Clozapine Clozapine may decrease the effect of Tramadol by decreasing active metabolite production.
          Cocaine Cocaine may decrease the effect of Tramadol by decreasing active metabolite production.
          Conivaptan Conivaptan may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Cyclobenzaprine Increases risk of seizure.
          Cyclosporine Cyclosporine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Darifenacin Darifenacin may decrease the effect of Tramadol by decreasing active metabolite production.
          Darunavir Darunavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Delavirdine Delavirdine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Delavirdine may decrease the effect of Tramadol by decreasing active metabolite production.
          Desipramine Tramadol increases the risk of serotonin syndrome and seizures. Desipramine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Desipramine may decrease the effect of Tramadol by decreasing active metabolite production.
          Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Dexamethasone Dexamethasone may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
          Dextroamphetamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Dextromethorphan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Dihydroergotamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Diltiazem Diltiazem may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Diphenhydramine Diphenhydramine may decrease the effect of Tramadol by decreasing active metabolite production.
          Doxepin Tramadol increases the risk of serotonin syndrome and seizures.
          Duloxetine Duloxetine may decrease the effect of Tramadol by decreasing active metabolite production. Increased risk of serotonin syndrome. Monitor for Tramadol efficacy and symptoms of serotonin syndrome.
          Efavirenz Efavirenz may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
          Eletriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Ergoloid mesylate Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Ergonovine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Ergotamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Erythromycin Erythromycin may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Escitalopram Tramadol may increase the risk of serotonin syndrome and seizures.
          Etravirine Tramadol,when used concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration and efficacy due to increased tramadol metabolism and clearance.
          Fluconazole Fluconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Fluoxetine The use of two serotonin modulators, such as fluoxetine and tramadol, may increase the risk of serotonin syndrome. Fluoxetine may decrease the effect of tramadol by decreasing active metabolite production.
          Fluvoxamine Tramadol may increase the risk of serotonin syndrome and seizures.
          Fosamprenavir Fosamprenavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Fosphenytoin Fosphenytoin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
          Frovatriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Furazolidone Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Furazolidone.
          Haloperidol Haloperidol may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Haloperidol may decrease the effect of Tramadol by decreasing active metabolite production.
          Imatinib Imatinib may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Imatinib may decrease the effect of Tramadol by decreasing active metabolite production.
          Imipramine Tramadol increases the risk of serotonin syndrome and seizures. Imipramine may decrease the effect of Tramadol by decreasing active metabolite production.
          Indinavir Indinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Isocarboxazid Tramadol may increase the risk of serotonin syndrome and seizure induction by the MAO inhibitor, isocarboxazid.
          Isoniazid Isoniazid may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Isoniazid may decrease the effect of Tramadol by decreasing active metabolite production.
          Itraconazole Itraconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Ketoconazole Ketoconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Ketoconazole may decrease the effect of Tramadol by decreasing active metabolite production.
          Lapatinib Lapatinib may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Lidocaine Lidocaine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Lidocaine may decrease the effect of Tramadol by decreasing active metabolite production.
          Linezolid Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Linezolid.
          Lisdexamfetamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Lopinavir Lopinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Lopinavir may decrease the effect of Tramadol by decreasing active metabolite production.
          Maprotiline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Meperidine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Methadone Methadone may decrease the effect of Tramadol by decreasing active metabolite production.
          Methamphetamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Methotrimeprazine Additive CNS depressant effects. Decrease dose of tramadol by 50% if initiating methotrimeprazine therapy. Monitor for increased CNS depression and apply further dosage adjustments as required.
          Methylergonovine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Metronidazole Metronidazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Miconazole Miconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Miconazole may decrease the effect of Tramadol by decreasing active metabolite production.
          Mirtazapine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Moclobemide Tramadol may increase the risk of serotonin syndrome and seizure induction by the MAO inhibitor, moclobemide.
          Nafcillin Nafcillin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
          Naratriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Nefazodone Nefazodone may increase tramadol toxicity by decreasing tramadol metabolism and clearance. Increased risk of serotonin syndrome. Monitor for tramadol toxicity and symptoms of serotonin syndrome.
          Nelfinavir Nelfinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Nevirapine Nevirapine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
          Nicardipine Nicardipine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Nicardipine may decrease the effect of Tramadol by decreasing active metabolite production.
          Nilotinib Nilotinib may decrease the effect of Tramadol by decreasing active metabolite production.
          Norfloxacin Norfloxacin may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Nortriptyline Tramadol increases the risk of serotonin syndrome and seizures.
          Oxcarbazepine Oxcarbazepine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
          Paroxetine Tramadol may increase the risk of serotonin syndrome and seizures. Paroxetine may decrease the effect of Tramadol by decreasing active metabolite production.
          Pentobarbital Pentobarbital may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
          Pergolide Pergolide may decrease the effect of Tramadol by decreasing active metabolite production. Increased risk of serotonin syndrome. Monitor for Tramadol efficacy and symptoms of serotonin syndrome.
          Phendimetrazine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Phenelzine Tramadol may increase the risk of serotonin syndrome and seizure induction by the MAO inhibitor, phenelzine.
          Phenobarbital Phenobarbital may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
          Phentermine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Phenytoin Phenytoin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
          Pioglitazone Pioglitazone may decrease the effect of Tramadol by decreasing active metabolite production.
          Posaconazole Posaconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Primidone Primidone may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
          Procarbazine Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Procarbazine.
          Promethazine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Protriptyline Tramadol increases the risk of serotonin syndrome and seizures.
          Pyrimethamine Pyrimethamine may decrease the effect of Tramadol by decreasing active metabolite production.
          Quinidine Quinidine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Quinidine may decrease the effect of Tramadol by decreasing active metabolite production.
          Quinine Quinine may decrease the effect of Tramadol by decreasing active metabolite production.
          Ranolazine Ranolazine may decrease the effect of Tramadol by decreasing active metabolite production.
          Rasagiline Tramadol may increase the risk of serotonin syndrome and seizure induction by the MAO inhibitor, rasagiline.
          Rifabutin Rifabutin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
          Rifampin Rifampin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
          Rifapentine Rifapentine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
          Ritonavir Ritonavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Ritonavir may decrease the effect of Tramadol by decreasing active metabolite production.
          Rizatriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          S-Adenosylmethionine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Saquinavir Saquinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Selegiline Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Selegiline.
          Sertraline Tramadol increases the risk of serotonin syndrome and seizures. Sertraline may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Sertraline may decrease the effect of Tramadol by decreasing active metabolite production.
          Sibutramine Sibutramine may incrase the serotonergic effect of the Tramadol. Concomitant therapy should be avoided.
          Sitaxentan Sitaxsentan may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          St. John's Wort Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Sumatriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Telithromycin Telithromycin may decrease the metabolism and clearance of tramadol. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of tramadol if telithromycin is initiated, discontinued or dose changed.
          Terbinafine Terbinafine may decrease the effect of Tramadol by decreasing active metabolite production.
          Tetracycline Tetracycline may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Thioridazine Thioridazine may decrease the effect of Tramadol by decreasing active metabolite production.
          Ticlopidine Ticlopidine may decrease the effect of Tramadol by decreasing active metabolite production.
          Tranylcypromine Tramadol may increase the risk of serotonin syndrome and seizure induction by the MAO inhibitor, tranylcypromine. Tranylcypromine may decrease the effect of tramadol by decreasing active metabolite production.
          Trazodone The use of two serotonin modulators, such as trazodone and tramadol, may increase the risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Trimipramine Tramadol may increase the risk of serotonin syndrome and seizures.
          Triprolidine The CNS depressants, Triprolidine and Tramadol, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
          Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
          Verapamil Verapamil may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
          Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of tramadol by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of tramadol if voriconazole is initiated, discontinued or dose changed.
          Zolmitriptan The use of two serotonin modulators, such as zolmitriptan and tramadol, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
          食物相互作用
          Not Available

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