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药品详细

Phenytoin(苯妥英钠)

化学结构式图
中文名
苯妥英钠
英文名
Phenytoin
分子式
C15H12N2O2
化学名
5,5-diphenylimidazolidine-2,4-dione
分子量
Average: 252.268
Monoisotopic: 252.089877638
CAS号
57-41-0
ATC分类
N03A 未知;N03A 未知;N03A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

An anticonvulsant that is used in a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [PubChem]

生产厂家
  • Actavis mid atlantic llc
  • Amneal pharmaceuticals ny llc
  • App pharmaceuticals llc
  • Barr laboratories inc
  • Baxter healthcare corp
  • Hikma farmaceutica (portugal) sa
  • Hospira inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Lannett co inc
  • Marsam pharmaceuticals llc
  • Mylan pharmaceuticals inc
  • Parke davis div warner lambert co
  • Parke davis pharmaceutical research div warner lambert co
  • Pfizer pharmaceuticals ltd
  • Pharmaforce inc
  • Pharmeral inc
  • Pliva inc
  • Smith and nephew solopak div smith and nephew
  • Solopak medical products inc
  • Sun pharmaceutical industries ltd
  • Taro pharmaceutical industries ltd
  • Vistapharm inc
  • Warner chilcott div warner lambert co
  • Watson laboratories inc
  • Wockhardt eu operations (swiss) ag
  • Wockhardt ltd
  • Wockhardt usa inc
封装厂家
参考
Synthesis Reference Not Available
General Reference Not Available
剂型
规格
化合物类型
Type small molecule
Classes
  • Diphenylmethanes
Substructures
  • Imidazolidinediones
  • Carboxylic Acids and Derivatives
  • Amino Ketones
  • Benzene and Derivatives
  • Ureas and Derivatives
  • Imidazolidines
  • Diphenylmethanes
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
适应症
药理
Indication For the control of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery.
Pharmacodynamics Phenytoin is an antiepileptic drug which can be useful in the treatment of epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of tonic-clonic (grand mal) seizures. Phenytoin acts to dampen the unwanted, runaway brain activity seen in seizure by reducing electrical conductance among brain cells. It lacks the sedation effects associated with phenobarbital. There are some indications that phenytoin has other effects, including anxiety control and mood stabilization, although it has never been approved for those purposes by the FDA. Phenytoin is primarily metabolized by CYP2C9.
Mechanism of action Phenytoin acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. By promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of post-tetanic potentiation at synapses. Loss of post-tetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas.
Absorption Bioavailability 70-100% oral, 24.4% for rectal and intravenous administration. Rapid rate of absorption with peak blood concentration expected in 1½ to 3 hours.
Volume of distribution Not Available
Protein binding Highly protein bound, 90%
Metabolism
Primarily hepatic

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

Substrate Enzymes Product
Phenytoin
3',4'-Dihydrodiol Details
Phenytoin
3'-HPPH Details
Phenytoin
4'-HPPH Details
Phenytoin
    		Hydroxyphenytoin Details
    Phenytoin
      		Hydroxyphenytoin-O-glucuronide Details
      Phenytoin
        		Phenytoin arene-oxide Details
        Phenytoin
          		Phenytoin catechol Details
          Phenytoin
            		Phenytoin dihydrodiol Details
            Phenytoin
              		Phenytoin methylcatechol Details
              Phenytoin
                		Phenytoin quinone Details
                Route of elimination Most of the drug is excreted in the bile as inactive metabolites which are then reabsorbed from the intestinal tract and excreted in the urine. Urinary excretion of phenytoin and its metabolites occurs partly with glomerular filtration but, more importantly, by tubular secretion.
                Half life 22 hours (range of 7 to 42 hours)
                Clearance Not Available
                Toxicity Oral, mouse: LD50 = 150 mg/kg; Oral, rat: LD50 = 1635 mg/kg. Symptoms of overdose include coma, difficulty in pronouncing words correctly, involuntary eye movement, lack of muscle coordination, low blood pressure, nausea, sluggishness, slurred speech, tremors, and vomiting.
                Affected organisms
                • Humans and other mammals
                Pathways
                Pathway Name SMPDB ID
                Smp00326 Fosphenytoin (Antiarrhythmic) Pathway SMP00326
                Smp00327 Phenytoin (Antiarrhythmic) Pathway SMP00327
                理化性质
                Properties
                State solid
                Experimental Properties
                Property Value Source
                melting point 286 °C PhysProp
                water solubility 32 mg/L (at 22 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
                logP 2.47 HANSCH,C ET AL. (1995)
                Caco2 permeability -4.57 ADME Research, USCD
                pKa 8.33 SANGSTER (1994)
                Predicted Properties
                Property Value Source
                water solubility 7.11e-02 g/l ALOGPS
                logP 2.26 ALOGPS
                logP 2.15 ChemAxon
                logS -3.5 ALOGPS
                pKa (strongest acidic) 9.47 ChemAxon
                pKa (strongest basic) -9 ChemAxon
                physiological charge 0 ChemAxon
                hydrogen acceptor count 2 ChemAxon
                hydrogen donor count 2 ChemAxon
                polar surface area 58.2 ChemAxon
                rotatable bond count 2 ChemAxon
                refractivity 70.18 ChemAxon
                polarizability 25.48 ChemAxon
                药物相互作用
                Drug Interaction
                Abiraterone Strong CYP3A4 inducers may decrease levels of abiraterone. Monitor concomitant therapy closely.
                Acenocoumarol Increased hydantoin levels and risk of bleeding
                ado-trastuzumab emtansine Avoid combination with phenytoin and other strong CYP3A4 inducers due to the likely increase in metabolism of ado-trastuzumab emtansine to its active component, DM1.
                Alprazolam Phenytoin may increase the metabolism of alprazolam via CYP3A4.
                Aminophylline Decreased effect of both products
                Amiodarone Amiodarone may increase the therapeutic and adverse effects of phenytoin.
                Anisindione Increased hydantoin levels and risk of bleeding
                Aprepitant The CYP3A4 inducer, phenytoin, may decrease the effect of aprepitant.
                Asenapine Phenytoin is a CYP1A2 inducer and may increase metabolism of asenapine.
                Atracurium Phenytoin decreases the effect of the muscle relaxant
                Axitinib Avoid combination with phenytoin and other strong, moderate, or weak CYP3A4 inducers due to the likely decreased levels of axitinib.
                Betamethasone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, betamethasone.
                Bleomycin The antineoplasic agent decreases the effect of hydantoin
                Boceprevir Strong CYP3A4 inducers will decrease levels of boceprevir. Concomitant therapy is contraindicated.
                Cabazitaxel Concomitant therapy with a strong CYP3A inducer may decrease concentrations of cabazitaxel. Avoid concomitant therapy.
                Canagliflozin Nonselective inducers of UGT enzymes may decrease levels of canagliflozin, thus decreasing efficacy. Consider increase the dose to 300 mg once daily.
                Capecitabine Capecitabine increases the effect of hydantoin
                Carboplatin The antineoplasic agent decreases the effect of hydantoin
                Carmustine The antineoplasic agent decreases the effect of hydantoin
                Chloramphenicol Increases phenytoin, modifies chloramphenicol
                Chlordiazepoxide Phenytoin may increase the metabolism of chlordiazepoxide via CYP3A4.
                Chlorotrianisene The enzyme inducer, phenytoin, decreases the effect of the hormone agent, chlorotrianisene.
                Chlorpheniramine The antihistamine increases the effect of hydantoin
                Cimetidine Cimetidine may increase the therapeutic effect of phenytoin.
                Ciprofloxacin Ciprofloxacin may decrease the therapeutic effect of phenytoin.
                Cisplatin The antineoplasic agent decreases the effect of hydantoin
                Clarithromycin Clarithromycin may increase the therapeutic and adverse effects of phenytoin.
                Clomifene The enzyme inducer, phenytoin, decreases the effect of the hormone agent, clomifene.
                Clorazepate Phenytoin may increase the metabolism of clorazepate via CYP3A4.
                Clozapine Phenytoin may decrease the effect of clozapine.
                Colesevelam Colesevelam may decrease the serum concentration of Phenytoin. Phenytoin should be administered at least 4 hours prior to colesevelam.
                Conjugated Estrogens The enzyme inducer, phenytoin, decreases the effect of the hormone agent, conjugated estrogens.
                Cortisone acetate The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, cortisone acetate.
                Cyclosporine The hydantoin decreases the effect of cyclosporine
                Dabrafenib Strong CYP3A4 inducers may decrease levels of dabrafenib. Consider alternate therapy.
                Dasatinib Phenytoin may decrease the serum level and efficacy of dasatinib.
                Delavirdine The anticonvulsant, phenytoin, decreases the effect of delavirdine.
                Dexamethasone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, dexamethasone.
                Diazepam Phenytoin may increase the metabolism of diazepam via CYP3A4.
                Diazoxide Diazoxide decreases the efficacy of phenytoin.
                Dicumarol Increased hydantoin levels and risk of bleeding
                Diethylstilbestrol The enzyme inducer, phenytoin, decreases the effect of the hormone agent, diethylstilbestrol.
                Disopyramide The hydantoin decreases the effect of disopyramide
                Disulfiram Disulfiram may increase the therapeutic and adverse effects of phenytoin.
                Dopamine Risk of severe hypotension
                Doxacurium chloride Phenytoin decreases the effect of the muscle relaxant
                Doxycycline The anticonvulsant, phenytoin, may decrease the effect of doxycycline.
                Dyphylline Decreased effect of both products
                Estradiol The enzyme inducer, phenytoin, decreases the effect of the hormone agent, estradiol.
                Estradiol valerate/Dienogest Affects CYP3A4 metabolism, decreases or effects levels of Estradiol valerate/Dienogest.
                Estriol The enzyme inducer, phenytoin, decreases the effect of the hormone agent, estriol.
                Estrone The enzyme inducer, phenytoin, decreases the effect of the hormone agent, estrone.
                Estropipate The enzyme inducer, phenytoin, decreases the effect of the hormone agent, estropipate.
                Ethinyl Estradiol This product may cause a slight decrease of contraceptive effect
                Etravirine Etravirine, when used concomitantly with phenytoin, may experience a decrease in serum concentration. It is recommended to avoid concurrent therapy.
                Ezogabine Ezogabine increases the clearance of phenytoin (30%). The mechanism of this interaction is unknown.
                Felbamate Increased phenytoin levels and decreased felbamate levels
                Felodipine The hydantoin decreases the effect of felodipine
                Fluconazole Fluconazole may increase the therapeutic and adverse effects of phenytoin.
                Fludrocortisone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, fludrocortisone.
                Fluorouracil Fluorouracil increases the effect of hydantoin
                Fluoxetine Fluoxetine increases the effect of phenytoin
                Flurazepam Phenytoin may increase the metabolism of flurazepam via CYP3A4.
                Fluvoxamine Fluvoxamine may increase the therapeutic effect of phenytoin.
                Folic Acid Folic acid may decrease the levels of phenytoin.
                Furosemide The hydantoin decreases the effect of furosemide
                Gabapentin Gabapentin may increase the therapeutic and adverse effects of phenytoin.
                Gefitinib The CYP3A4 inducer, phenytoin, may decrease the serum concentration and therapeutic effects of gefitinib.
                Hydrocortisone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, hydrocortisone.
                Imatinib The hydantoin decreases the levels of imatinib
                Irinotecan The hydantoin decreases the effect of irinotecan
                Isoniazid Isoniazid increases the effect of phenytoin in 20% of patients
                Itraconazole Phenytoin decreases the effect of itraconazole
                Ivacaftor Strong CYP3A4 inducers may decrease levels of ivacaftor. Monitor concomitant therapy closely.
                Lamotrigine Phenytoin may reduce levels of lamotrigine
                Levodopa The hydantoin decreases the effect of levodopa
                Levonorgestrel Phenytoin decreases the contraceptive effect
                Lopinavir Levels of both drugs are affected
                Mebendazole The hydantoin decreases the efficiency of mebendazole
                Medroxyprogesterone The enzyme inducer, phenytoin, may decrease the effect of medroxyprogesterone.
                Megestrol The enzyme inducer, phenytoin, may decrease the effect of megestrol.
                Mestranol This product may cause a slight decrease of contraceptive effect
                Methadone The hydantoin decreases the effect of methadone
                Methotrexate The antineoplasic agent decreases the effect of hydantoin
                Methoxsalen The hydantoin decreases the effect of psoralene
                Methylprednisolone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, methylprednisolone.
                Metocurine Phenytoin decreases the effect of the muscle relaxant
                Metyrapone The combination renders the test invalid
                Mexiletine The hydantoin decreases the effect of mexiletine
                Midazolam Phenytoin may increase the metabolism of midazolam via CYP3A4.
                Mirtazapine The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects
                Mivacurium Phenytoin decreases the effect of the muscle relaxant
                Nisoldipine Phenytoin decreases the efficiency of nisoldipine
                Norethindrone This product may cause a slight decrease of contraceptive effect
                Omeprazole Omeprazole increases the effect of hydantoin
                Oxcarbazepine Oxcarbazepine increases the effect of hydantoin
                Oxtriphylline Decreased effect of both products
                Oxyphenbutazone The NSAID, oxphenbutazone, may increase the therapeutic and adverse effects of phenytoin.
                Pancuronium Phenytoin decreases the effect of the muscle relaxant
                Paramethasone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, paramethasone.
                Perampanel Avoid combination with phenytoin or other strong CYP3A4 inducers due to the likely decrease of perampanel concentration. If the combination must be used, an increase in perampanel dose is necessary.
                Phenylbutazone The NSAID, phenylbutazone, may increase the therapeutic and adverse effects of phenytoin.
                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.
                Posaconazole Modifications of drug levels for both agents
                Praziquantel Markedly lower praziquantel levels
                Prednisolone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, prednisolone.
                Prednisone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, prednisone.
                Quetiapine Phenytoin decreases the effect of quetiapine
                Quinestrol The enzyme inducer, phenytoin, decreases the effect of the hormone agent, quinestrol.
                Quinidine The anticonvulsant, phenytoin, decreases the effect of quinidine.
                Regorafenib Strong CYP3A4 inducers may decrease levels of regorafenib.
                Rifampin Rifampin may decrease the therapeutic and adverse effects of phenytoin.
                Rilpivirine Strong inducers of CYP3A4 decrease the exposure of rilpivirine thus decreasing efficacy.
                Rufinamide Increases clearance of rufinamide thus decreasing plasma concentration of rufinamide.
                Sertraline Sertraline increases the effect of hydantoin
                Sirolimus The hydantoin decreases sirolimus levels
                Sucralfate Sucralfate decreases the effect of hydantoin
                Sulfadiazine The sulfonamide increases the effect of hydantoin
                Sulfamethizole The sulfonamide increases the effect of hydantoin
                Sunitinib Possible decrease in sunitinib levels
                Tacrolimus Phenytoin may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Phenytoin therapy is initiated, discontinued or altered.
                Telithromycin Phenytoin may decrease the plasma concentration of Telithromycin by increasing its metabolism. Consider alternate therapy.
                Temsirolimus Phenytoin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
                Theophylline Decreased effect of both products
                Thiotepa Possible increase in thiotepa levels
                Ticlopidine Ticlopidine may decrease the metabolism and clearance of phenytoin. Consider alternate therapy or monitor for adverse/toxic effects of phenytoin if ticlopidine is initiated, discontinued or dose changed.
                Tipranavir Phenytoin decreases the concentration of Tipranavir. Monitor for decreased Tipranavir efficacy.
                Tobramycin Increased risk of nephrotoxicity
                Tofacitinib Avoid combination with phenytoin and other strong CYP3A4 inducers due to the potential decrease in tofacitinib serum levels.
                Tolbutamide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Phenytoin. Consider alternate therapy or monitor for changes in Phenytoin therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
                Tolvaptan Phenytoin is a CYP3A4 inducer and will decrease serum concentrations of tolvaptan and ultimately, its clinical effects.
                Topiramate Increased phenytoin/decreased topiramate
                Tramadol Phenytoin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
                Trazodone The CYP3A4 inducer, Phenytoin, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Phenytoin is initiated, discontinued or dose changed.
                Tretinoin The strong CYP2C8 inducer, Phenytoin, 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 Phenytoin is initiated, discontinued or dose changed.
                Triamcinolone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, triamcinolone.
                Triazolam Phenytoin may increase the metabolism of triazolam via CYP3A4.
                Trimethoprim Trimethoprim increases the effect of hydantoin
                Trioxsalen The hydantoin decreases the effect of psoralene
                Triprolidine The CNS depressants, Triprolidine and Phenytoin, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
                Tubocurarine Phenytoin decreases the effect of the muscle relaxant
                Ulipristal Concomitant therapy with strong CYP3A4 inducers may decrease plasma concentrations of ulipristal and ultimately its effectiveness. Avoid combination therapy.
                Vandetanib Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
                Vecuronium Phenytoin decreases the effect of the muscle relaxant
                Vemurafenib Strong CYP3A4 inducers may decrease levels of vemurafenib. Monitor concomitant therapy closely.
                Verapamil Verapamil may increase the serum concentration of Phenytoin by decreasing its metabolism. Monitor for changes in the therapeutic/adverse effects of Phenytoin if Verapamil is initiated, discontinued or dose changed.
                Vigabatrin Vigabatrin reduces plasma levels of phenytoin by 16-20% which may be due to induction of CYP2C. Consider dosage adjustment.
                Vinblastine The antineoplasic agent decreases the effect of hydantoin
                Voriconazole Voriconazole may increase the serum concentration of phenytoin by decreasing its metabolism. Phenytoin may increase the serum concentration of voriconazole by increasing its metabolism. Consider alternate antifungal therapy or monitor for voriconazole therapy failure and phenytoin toxicity.
                Warfarin Warfarin may increase the serum concentration of phenytoin possibly by competing for CYP2C9 metabolism. Phenytoin may increase the anticoagulant effect of warfarin. Monitor phenytoin levels, prothrombin time, and therapeutic and adverse effects of both agents during concomitant therapy.
                食物相互作用
                • Avoid alcohol.
                • Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication.
                • Take with food to increase bioavailability and reduce irritation.

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