Tìm theo
Phenytoin
Các tên gọi khác (9 ) :
  • 5,5-Diphenyl-imidazolidine-2,4-dione
  • 5,5-diphenylimidazolidine-2,4-dione
  • 5,5-diphenyltetrahydro-1H-2,4-imidazoledione
  • 5,5-Diphenyltetrahydro-1H-2,4-imidazoledione
  • DILANTIN
  • Fenitoina
  • PHENTYTOIN
  • Phenytoine
  • Phenytoinum
Thuốc điều trị về tâm thần
Thuốc Gốc
Small Molecule
CAS: 57-41-0
ATC: N03AB02, N03AB04, N03AB05
ĐG : Actavis Group , http://www.actavis.com
CTHH: C15H12N2O2
PTK: 252.268
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]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C15H12N2O2
Phân tử khối
252.268
Monoisotopic mass
252.089877638
InChI
InChI=1S/C15H12N2O2/c18-13-15(17-14(19)16-13,11-7-3-1-4-8-11)12-9-5-2-6-10-12/h1-10H,(H2,16,17,18,19)
InChI Key
InChIKey=CXOFVDLJLONNDW-UHFFFAOYSA-N
IUPAC Name
5,5-diphenylimidazolidine-2,4-dione
Traditional IUPAC Name
phenytoin
SMILES
O=C1NC(=O)C(N1)(C1=CC=CC=C1)C1=CC=CC=C1
Độ tan chảy
286 °C
Độ hòa tan
32 mg/L (at 22 °C)
logP
2.47
logS
-3.5
pKa (strongest acidic)
9.47
pKa (Strongest Basic)
-9
PSA
58.2 Å2
Refractivity
70.18 m3·mol-1
Polarizability
25.48 Å3
Rotatable Bond Count
2
H Bond Acceptor Count
2
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
caco2 Permeability
-4.57
pKa
8.33
Dược Lực Học : 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.
Cơ Chế Tác Dụng : 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] 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.
Dược Động Học :
▧ 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.
▧ Protein binding :
Highly protein bound, 90%
▧ Metabolism :
Primarily hepatic. The majority of the dose (up to 90%) is metabolized to 5-(4'-hydroxyphenyl)-5-phenylhydantoin (p-HPPH). This metabolite undergoes further glucuronidation and is excreted into the urine. CYP2C19 and CYP2C9 catalyze the aforementioned reaction.
▧ 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)
Độc Tính : 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.
Chỉ Định : 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.
Tương Tác Thuốc :
  • 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.
  • Chlorphenamine 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.
  • Dicoumarol 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.
  • L-DOPA The hydantoin decreases the effect of levodopa
  • Lamotrigine Phenytoin may reduce levels of lamotrigine
  • Levonorgestrel Phenytoin decreases the contraceptive effect
  • Lopinavir Levels of both drugs are affected
  • Mebendazole The hydantoin decreases the efficiency of mebendazole
  • Medroxyprogesterone Acetate The enzyme inducer, phenytoin, may decrease the effect of medroxyprogesterone.
  • Megestrol acetate 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.
  • Rifampicin 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.
Liều Lượng & Cách Dùng : Capsule - Oral - 30 mg, 100 mg, 200 mg, 300 mg
Injection, solution - Oral - 50 mg/mL
Tablet - Oral - 125 mg/5 mL
Tablet, chewable - Oral - 50 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Dilantin
  • Công ty :
    Sản phẩm biệt dược : Dilantin-125
  • Công ty : Pfizer
    Sản phẩm biệt dược : Epanutin
  • Công ty :
    Sản phẩm biệt dược : Eptoin
  • Sản phẩm biệt dược : Phenytek
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00252
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=1775
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508847
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07443
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00512
ChemSpider
http://www.chemspider.com/Chemical-Structure.1710.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/51672-4069-1
PharmGKB
http://www.pharmgkb.org/drug/PA450947
Wikipedia
http://en.wikipedia.org/wiki/Phenytoin
RxList
http://www.rxlist.com/cgi/generic/phenyt.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/dil1136.shtml
Drugs.com
http://www.drugs.com/cdi/phenytoin.html
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