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药品详细

Carbamazepine(卡马西平)

化学结构式图
中文名
卡马西平
英文名
Carbamazepine
分子式
C15H12N2O
化学名
2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaene-2-carboxamide
分子量
Average: 236.2686
Monoisotopic: 236.094963016
CAS号
298-46-4
ATC分类
N03A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [PubChem]

生产厂家
  • Actavis elizabeth llc
  • Apotex inc etobicoke site
  • Cadista pharmaceuticals inc
  • Inwood laboratories inc sub forest laboratories inc
  • Novartis pharmaceuticals corp
  • Pliva inc
  • Shire development inc
  • Taro pharmaceutical industries ltd
  • Taro pharmaceuticals usa inc
  • Teva pharmaceuticals usa inc
  • Torrent pharmaceuticals ltd
  • Usl pharma inc
  • Validus pharmaceuticals inc
  • Warner chilcott div warner lambert co
  • Wockhardt eu operations (swiss) ag
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Staines AG, Coughtrie MW, Burchell B: N-glucuronidation of carbamazepine in human tissues is mediated by UGT2B7. J Pharmacol Exp Ther. 2004 Dec;311(3):1131-7. Epub 2004 Aug 3. Pubmed
  2. Sisodiya SM, Goldstein DB: Drug resistance in epilepsy: more twists in the tale. Epilepsia. 2007 Dec;48(12):2369-70. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Dibenzazepines and Derivatives
Substructures
  • Alkanes and Alkenes
  • Dibenzazepines and Derivatives
  • Phenylpropenes
  • Benzene and Derivatives
  • Ureas and Derivatives
  • Carbamates and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Azepines
  • Benzazepines
  • Anilines
适应症
药理
Indication For the treatment of epilepsy and pain associated with true trigeminal neuralgia.
Pharmacodynamics Carbamazepine, an anticonvulsant structurally similar to tricyclic antidepressants, is used to treat partial seizures, tonic-clonic seizures, pain of neurologic origin such as trigeminal neuralgia, and psychiatric disorders including manic-depressive illness and aggression due to dementia. The response to carbamazepine is variable and may be due to its variable transport, especially across the blood-brain-barrier. The transporter that may confer drug resistance is RALBP1.
Mechanism of action Carbamazepine inhibits sustained repetitive firing by blocking use-dependent sodium channels. Pain relief is believed to be associated with blockade of synaptic transmission in the trigeminal nucleus and seizure control with reduction of post-tetanic potentiation of synaptic transmission in the spinal cord. Carbamazepine also possesses anticholinergic, central antidiuretic, antiarrhythmic, muscle relaxant, antidepressant (possibly through blockade of norepinephrine release), sedative, and neuromuscular-blocking properties.
Absorption In clinical studies, carbamazepine suspension, conventional tablets, and extended-release tablets delivered equivalent amounts of drug to the systemic circulation. However, it has been observed that the suspension is somewhat faster absorbed. Furthermore, the extended-release tablet is slightly slower than the conventional tablet. The bioavailability of the extended-release tablet is 89%, compared to the suspension. Plasma levels of carbamazepine are variable. The time to peak concentration for the different formulations are as follows: Suspension = 1.5 hours; Conventional tablets = 4-5 hours; Extended-release tablets = 3-12 hours.
Volume of distribution Not Available
Protein binding 76% bound to plasma proteins.
Metabolism
Hepatic. CYP3A4 is the primary isoform responsible for the formation of carbamazepine-10,11-epoxide. This metabolite is active and shown to be equipotent to carbamazepine as an anticonvulsant. Carbamazepine is more rapidly metabolized to the aforementioned metabolite in younger patients than in adults. It also undergoes glucuronidation via UGT2B7, however this finding has been disputed.

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

Substrate Enzymes Product
Carbamazepine
10,11-Epoxycarbamazepine Details
Carbamazepine
    		2-hydroxycarbamazepine Details
    Carbamazepine
      		2-hydroxyiminostilbene Details
      Carbamazepine
        		3-hydroxycarbamazepine Details
        Carbamazepine
          		Carbamazepine 2,3-epoxide Details
          Carbamazepine
            		Carbamazepine catechol Details
            Carbamazepine
              		Carbamazepine diol Details
              Carbamazepine
                		Carbamazepine-O-quinone Details
                Carbamazepine
                  		Iminoquinone Details
                  Route of elimination 72% of the dose is in the urine while 28% is in the feces. Hydroxylated and conjugated metabolites are largely what was recovered in the urine. 3% of the dose is recovered as unchanged carbamazepine.
                  Half life Initial half-life values range from 25-65 hours, decreasing to 12-17 hours on repeated doses.
                  Clearance Not Available
                  Toxicity Mild ingestions cause vomiting, drowsiness, ataxia, slurred speech, nystagmus, dystonic reactions, and hallucinations. Severe intoxications may produce coma, seizures, respiratory depression, and hypotension
                  Affected organisms
                  • Humans and other mammals
                  Pathways Not Available
                  理化性质
                  Properties
                  State solid
                  Experimental Properties
                  Property Value Source
                  melting point 190.2 °C PhysProp
                  water solubility 17.7 mg/L Not Available
                  logP 2.45 DAL POZZO,A ET AL. (1989)
                  Predicted Properties
                  Property Value Source
                  water solubility 1.52e-01 g/l ALOGPS
                  logP 2.1 ALOGPS
                  logP 2.77 ChemAxon
                  logS -3.2 ALOGPS
                  pKa (strongest acidic) 15.96 ChemAxon
                  pKa (strongest basic) -3.8 ChemAxon
                  physiological charge 0 ChemAxon
                  hydrogen acceptor count 1 ChemAxon
                  hydrogen donor count 1 ChemAxon
                  polar surface area 46.33 ChemAxon
                  rotatable bond count 0 ChemAxon
                  refractivity 71.89 ChemAxon
                  polarizability 25 ChemAxon
                  药物相互作用
                  Drug Interaction
                  Abiraterone Strong CYP3A4 inducers may decrease levels of abiraterone. Monitor concomitant therapy closely.
                  Acenocoumarol Carbamazepine may decrease the anticoagulant effect of acenocoumarol by decreasing its serum concentration.
                  Alprazolam Carbamazepine may decrease the effect of the benzodiazepine, alprazolam.
                  Aminophylline Carbamazepine may decrease the serum concentration of aminophylline. Aminophylline may decrease the serum concentration of carbamazepine. Monitor for changes in the therapeutic effect of both agents if concomitant therapy is initiated, discontinued or dose changed.
                  Amitriptyline Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if carbamazepine is initiated, discontinued or dose changed.
                  Anisindione Carbamazepine may decrease the anticoagulant effect of anisindione by decreasing its serum concentration.
                  Aprepitant The CYP3A4 inducer, carbamazepine, may decrease the effect of aprepitant.
                  Aripiprazole Carbamazepine, a strong CYP3A4 inducer, may decrease the serum concentration of aripiprazole by increasing its metabolism.
                  Asenapine Carbamazepine is a CYP1A2 inducer that decreases asenapine's exposure by 20%.
                  Atorvastatin Carbamazepine, a p-glycoprotein inducer and strong CYP3A4 inducer, may decrease the effect of atorvastatin by increasing its efflux and metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if carbamazepine is initiated, discontinued or dose changed.
                  Atracurium Decreases the effect of muscle relaxant
                  Bendamustine Decreases levels of bendamustine by affecting CYP1A2 hepatic enzyme metabolism. May increase concentrations of active metabolites.
                  Boceprevir Strong CYP3A4 inducers will decrease levels of boceprevir. Concomitant therapy is contraindicated.
                  Bupropion Carbamazepine, a strong CYP2B6 inducer, may increase the metabolism of bupropion. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bupropion if carbamazepine is initiated, discontinued or dose changed.
                  Cabazitaxel Concomitant therapy with a strong CYP3A inducer may decrease concentrations of cabazitaxel. Avoid concomitant therapy.
                  Cimetidine Cimetidine may increase the serum concentration of carbamazepine during the first few days of concomitant therapy. Monitor for changes in the therapeutic and adverse effects of carbamazepine if cimetidine is initiated, discontinued or dose changed.
                  Clarithromycin Clarithromycin may decrease the metabolism of carbamazepine. Monitor for changes in the therapeutic or adverse effects of carbamazepine if clarithromycin is initiated, discontinued or dose changed.
                  Clozapine Carbamazepine may decrease the serum concentration of clozapine by increasing its metabolism. Concomitant therapy should also be avoided due to increased risk of bone marrow suppression. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of clozapine if carbamazepine is initiated, discontinued or dose changed.
                  Cyclosporine Carbamazepine may decrease the therapeutic effect of cyclosporine.
                  Dabigatran etexilate P-Glycoprotein inducers such as carbamazepine may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.
                  Dabrafenib Strong CYP3A4 inducers may decrease levels of dabrafenib. Consider alternate therapy.
                  Danazol Danazol may decrease the metabolism of carbamazepine. Monitor for changes in the therapeutic and adverse effects of carbamazepine if danazol is initiated, discontinued or dose changed.
                  Delavirdine The anticonvulsant, carbamazepine, decreases the effect of delavirdine.
                  Desipramine Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, desipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if carbamazepine is initiated, discontinued or dose changed.
                  Dicumarol Carbamazepine may decrease the anticoagulant effect of dicumarol by decreasing its serum concentration.
                  Diltiazem Carbamazepine may decrease the serum concentration of diltiazem by increasing its metabolism. Diltiazem may increase the serum concentration of carbamazepine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if dosages are changed.
                  Doxacurium chloride Decreases the effect of muscle relaxant
                  Doxepin Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, doxepin, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if carbamazepine is initiated, discontinued or dose changed.
                  Doxycycline The anticonvulsant, carbamazepine, may decrease the therapeutic effect of doxycycline.
                  Dyphylline Carbamazepine may decrease the serum concentration of diphylline. Diphylline may decrease the serum concentration of carbamazepine. Monitor for changes in the therapeutic effect of both agents if concomitant therapy is initiated, discontinued or dose changed.
                  Eltrombopag Affects hepatic CYP1A2 metabolism, will decrease effect/level of eltrombopag. Affects hepatic CYP2C9/10 metabolism, will decrease effect/level of eltrombopag.
                  Erythromycin The macrolide, erythromycin, may increase the effect of carbamazepine.
                  Estradiol valerate/Dienogest Affects CYP3A4 metabolism, decreases or effects levels of Estradiol valerate/Dienogest.
                  Ethinyl Estradiol Carbamazepine may decrease the contraceptive effect of ethinyl estradiol. Hormonal contraception should not be relied on alone during concomitant therapy with carbamazepine.
                  Etravirine Carbamazepine, when used concomitantly with certain NNRTIs (ie. efavirenz), may experience a decrease in serum concentration. Etravirine, and other NNRTIs, when used concomitantly with carbamazepine, may experience an increase in serum concentration. It is recommended to avoid this combination.
                  Ezogabine Ezogabine increases the clearance of carbamazepine (30%). The mechanism of this interaction is unknown.
                  Felbamate Decreased effect of both products
                  Felodipine Carbamazepine may increase the metabolism of felodipine. Monitor for changes in the therapeutic and adverse effects of felodipine if carbamazepine is initiated, discontinued or dose changed.
                  Fluconazole Fluconazole may increase the therapeutic and adverse effects of carbamazepine.
                  Fluoxetine Carbamazepine may decrease the serum concentration of fluoxetine by increasing its metabolism. Fluoxetine may increase the serum concentration of carbamazepine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or doses are changed.
                  Fluvoxamine Fluvoxamine increases the effect of carbamazepine
                  Gefitinib The CYP3A4 inducer, carbamazepine, may decrease the serum concentration and therapeutic effects of gefitinib.
                  Haloperidol Carbamazepine may decrease the serum concentration of haloperidol by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of haloperidol if carbamazepine is initiated, discontinued or dose changed.
                  Imatinib Carbamazepine, a strong CYP3A4 inducer, may increase the metabolism of imatinib. Imatinib, a strong CYP3A4 inhibitor, may increase the metabolism of carbamazepine. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or dose changed.
                  Imipramine Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, imipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if carbamazepine is initiated, discontinued or dose changed.
                  Indinavir Indinavir increases the effect and toxicity of carbamazepine
                  Isoniazid Carbamazepine effect is increased as is isoniazid toxicity
                  Isotretinoin Isotretinoine decreases the effect of carbamazepine
                  Itraconazole Itraconazole may increase the effect of carbamazepine.
                  Ivacaftor Strong CYP3A4 inducers may decrease levels of ivacaftor. Monitor concomitant therapy closely.
                  Josamycin The macrolide, josamycin, may increase the effect of carbamazepine.
                  Ketoconazole Ketoconazole may increase the effect of carbamazepine.
                  Lamotrigine Lamotrigine may increase the adverse effects of carbamazepine by increasing the concentration of its active metabolite, carbamazepine-epoxide. Carbamazepine may decrease the therapeutic effect of lamotrigine by increasing its metabolism. Lamotrigine doses should be adjusted accordingly. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinue or doses are changed.
                  Levetiracetam Concomitant therapy may results in additive adverse CNS effects.
                  Levonorgestrel Carbamazepine may decrease the contraceptive effect of levonorgestrel.
                  Linagliptin CYP3A4 and p-glycoprotein inducers may decreases levels of linagliptin. Monitor concomitant therapy closely.
                  Lovastatin Carbamazepine, a p-glycoprotein inducer and strong CYP3A4 inducer, may decrease the effect of lovastatin by increasing its efflux and metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if carbamazepine is initiated, discontinued or dose changed.
                  Lurasidone Concomitant therapy with a CYP3A4 inducer will decrease levels of lurasidone. Coadministration with lurasidone is contraindicated.
                  Mestranol This product may cause a slight decrease of contraceptive effect
                  Methadone Carbamazepine may decrease the serum level of methadone. Monitor for changes in the therapeutic and adverse effects of methadone if carbamazepine is initiated, discontinued or dose changed.
                  Methylphenidate Carbamazepine may decrease the effect of methylphendiate.
                  Metocurine Decreases the effect of muscle relaxant
                  Metronidazole Metronidazole increases the effect of carbamazepine
                  Midazolam Carbamazepine may decrease the effect of the benzodiazepine, midazolam.
                  Mivacurium Decrease the effect of muscle relaxant
                  Nefazodone Nefazodone increases the effect of carbamazepine
                  Norethindrone This product may cause a slight decrease of contraceptive effect
                  Nortriptyline Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if carbamazepine is initiated, discontinued or dose changed.
                  Oxtriphylline Carbamazepine may decrease the serum concentration of oxtriphylline. Oxtriphylline may decrease the serum concentration of carbamazepine. Monitor for changes in the therapeutic effect of both agents if concomitant therapy is initiated, discontinued or dose changed.
                  Oxybutynin Oxybutynin may cause carbamazepine toxicity
                  Pancuronium Decreases the effect of muscle relaxant
                  Pazopanib Affects CYP3A4 metabolism therefore will decrease levels or effect of pazopanib. Consider alternate therapy.
                  Ponatinib Strong CYP3A4 inducers may decrease levels of ponatinib. Monitor concomitant therapy closely.
                  Ponatinib Strong CYP3A4 inducers may decrease levels of ponatinib. Monitor concomitant therapy closely.
                  Praziquantel Markedly lower praziquantel levels
                  Propoxyphene Propoxyphene increases the effect of carbamazepine
                  Quinupristin This combination presents an increased risk of toxicity
                  Regorafenib Strong CYP3A4 inducers may decrease levels of regorafenib.
                  Rilpivirine Strong inducers of CYP3A4 decrease the exposure of rilpivirine thus decreasing efficacy.
                  Risperidone Decreases the effect of risperidone
                  Ritonavir Ritonavir increases the effect of carbamazepine
                  Roflumilast Affects CYP3A4 metabolism, decreases level or effect of roflumilast. Also decreases the level or effect of roflumilast by affecting CYP1A2 metabolism.
                  Rufinamide Decrease concentration of rufinamide thus monitor therapy
                  Sertraline Sertraline increases the effect of carbamazepine
                  Simvastatin Carbamazepine, a p-glycoprotein inducer, may decrease the effect of simvastatin by increasing its efflux. Monitor for changes in the therapeutic and adverse effects of simvastatin if carbamazepine is initiated, discontinued or dose changed.
                  Sunitinib Possible decrease in sunitinib levels
                  Tacrolimus Carbamazepine may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Carbamazepine therapy is initiated, discontinued or altered.
                  Telithromycin Co-administration may cause decreased Telithromycin and increased Carbemazepine plasma concentrations. Consider alternate therapy.
                  Temsirolimus Carbamazepine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
                  Theophylline Carbamazepine may decrease the serum concentration of theophylline. Theophylline may decrease the serum concentration of carbamazepine. Monitor for changes in the therapeutic effect of both agents if concomitant therapy is initiated, discontinued or dose changed.
                  Ticlopidine Ticlopidine increases the effect of carbamazepine
                  Tipranavir Concomitant use may result in decreased Tipranavir and increased Carbamazepine concentrations.
                  Tolvaptan Carbamazepine is a CYP3A4 inducer and will decrease serum concentrations of tolvaptan and ultimately, its clinical effects.
                  Topiramate Carbamazepine may decrease the effectiveness of Topiramate by increase its clearance. Monitor for changes in the therapeutic and adverse effects of Topiramate if Carbamazepine is initiated, discontinued or dose changed. Adverse effects related to CNS depression have also been observed during concomitant therapy.
                  Tramadol Carbamazepine may decrease the effect of tramadol by increasing Tramadol metabolism and clearance.
                  Trazodone The CYP3A4 inducer, Carbamazepine, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Carbamazepine is initiated, discontinued or dose changed.
                  Tretinoin The strong CYP2C8 inducer, Carbamazepine, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Carbamazepine is initiated, discontinued or dose changed.
                  Triprolidine The CNS depressants, Triprolidine and Carbamazepine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
                  Troleandomycin The macrolide, troleandomycin, may increase the effect of carbamazepine.
                  Tubocurarine Decreases the effect of muscle relaxant
                  Ulipristal Concomitant therapy with strong CYP3A4 inducers may decrease plasma concentrations of ulipristal and ultimately its effectiveness. Avoid combination therapy.
                  Valproic Acid Decreases the effect of valproic acid
                  Vandetanib Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
                  Vecuronium Decreases the effect of muscle relaxant
                  Vemurafenib Strong CYP3A4 inducers may decrease levels of vemurafenib. Monitor concomitant therapy closely.
                  Verapamil Verapamil may increase the serum concentration of Carbamazepine by decreasing its metabolism. Monitor for changes in the therapeutic/adverse effects of Carbamazepine if Verapamil is initiated, discontinued or dose changed.
                  Vilazodone Carbamazepine may increase the metabolism of Selective Serotonin Reuptake Inhibitors (SSRI). Specifically those agents metabolized via CYP1A2, 2C, and/or 3A4 isoenzymes. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Carbamazepine. Specifically those SSRIs that inhibit CYP3A4 isoenzymes.
                  Voriconazole Carbamazepine may reduce serum concentrations and efficacy of voriconazole likely by increasing its metabolism. Concomitant voriconazole and carbamazepine therapy is contraindicated.
                  Warfarin Carbamazepine may decrease the anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic and adverse effects of warfarin if carbamazepine is initiated, discontinued or dose changed.
                  Ziprasidone Increases the effect and toxicity of ziprasidone
                  食物相互作用
                  • Avoid alcohol.
                  • Avoid taking grapefruit or grapefruit juice throughout treatment.
                  • Grapefruit can significantly increase serum levels of this product.
                  • Take with food, increases availability and reduces irritation.

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