Banner
Identification
Name Phenytoin
Accession Number DB00252 (APRD00241)
Type small molecule
Groups approved
Description

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]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
5,5-diphenylhydantoin
5,5-Dwufenylohydantoina
Difenilhidantoina [Spanish]
Dihydantoin
Diphenylan Sodium
Diphenylhydantoin
Diphenylhydantoine [French]
Diphenylhydatanoin
Fenitoina [INN-Spanish]
Phenytoin Sodium
Phenytoine
Phenytoine [INN-French]
Phenytoinum [INN-Latin]
First Prev Next Last
Salts Not Available
Brand names
Name Company
Aleviatin
Antisacer
Auranile
Causoin
Citrullamon
Citrulliamon
Comital
Comitoina
Convul
Danten
Dantinal
Dantoinal
Dantoinal klinos
Dantoine
Denyl
Di-Hydan
Di-Lan
Di-Phetine
Didan TDC 250
Difenilhidantoina
Difenin
Difetoin
Difhydan
Dihycon
Dilabid
Dilantin
Dilantin acid
Dilantin-125
Dilantine
Dillantin
Dintoin
Dintoina
Diphantoin
Diphedal
Diphedan
Diphenat
Diphenin
Diphenine
Diphentoin
Diphentyn
Diphenylan
Ditoinate
Ekko
Elepsindon
Enkelfel
Epamin
Epanutin
Epasmir 5
Epdantoin Simple
Epdantoine simple
Epelin
Epifenyl
Epihydan
Epilan
Epilan D
Epilan-D
Epilantin
Epinat
Epised
Eptal
Eptoin
Fenantoin
Fenidantoin s
Fentoin
Fenylepsin
Fenytoin Dak
Fenytoine
Gerot-epilan-D
Hidan
Hidantal
Hidantilo
Hidantina
Hidantina senosian
Hidantina vitoria
Hidantomin
Hindatal
Hydantal
Hydantin
Hydantoin
Hydantoinal
Hydantol
Ictalis simple
Idantoil
Idantoin
Iphenylhydantoin
Kessodanten
Labopal
Lehydan
Lepitoin
Lepsin
Mesantoin
Minetoin
Neos-Hidantoina
Neosidantoina
Novantoina
Novophenytoin
Om hidantoina simple
Om-Hydantoine
Oxylan
Phanantin
Phanatine
Phenatine
Phenatoine
Phenhydan
Phenhydanin
Phenitoin
Phentoin
Phentytoin
Phenytex
Phenytoin AWD
Phenytoin-Gerot
Prompt Phenytoin Sodium
Ritmenal
Saceril
Sanepil
Silantin
Sinergina
Sodanthon
Sodantoin
Sodanton
Solantin
Solantoin
Solantyl
Sylantoic
Tacosal
Thilophenyl
TOIN
Toin unicelles
Zentronal
Zentropil
First Prev Next Last
Brand mixtures
Brand Name Ingredients
Dilantin W Phenobarbital 15mg Phenobarbital + Phenytoin Sodium
Dilantin W Phenobarbital 30mg Cap Phenobarbital + Phenytoin Sodium
Categories
  • Anticonvulsants
CAS number 57-41-0
Weight Average: 252.268
Monoisotopic: 252.089877638
Chemical Formula C15H12N2O2
InChI Key InChIKey=CXOFVDLJLONNDW-UHFFFAOYSA-N
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)
Plain Text
IUPAC Name
5,5-diphenylimidazolidine-2,4-dione
SMILES
O=C1NC(=O)C(N1)(C1=CC=CC=C1)C1=CC=CC=C1
Plain Text
Mass Spec show (9.46 KB)
Taxonomy
Kingdom Organic
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
Pharmacology
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
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
Pharmacoeconomics
Manufacturers
  • Parke davis div warner lambert co
  • Actavis mid atlantic llc
  • Taro pharmaceutical industries ltd
  • Vistapharm inc
  • Wockhardt eu operations (swiss) ag
  • Pfizer pharmaceuticals ltd
  • Lannett co inc
  • Amneal pharmaceuticals ny llc
  • Barr laboratories inc
  • Mylan pharmaceuticals inc
  • Pliva inc
  • Sun pharmaceutical industries ltd
  • Wockhardt ltd
  • Wockhardt usa inc
  • Watson laboratories inc
  • Pharmeral inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Parke davis pharmaceutical research div warner lambert co
  • App pharmaceuticals llc
  • Baxter healthcare corp
  • Hikma farmaceutica (portugal) sa
  • Hospira inc
  • Marsam pharmaceuticals llc
  • Pharmaforce inc
  • Smith and nephew solopak div smith and nephew
  • Solopak medical products inc
  • Warner chilcott div warner lambert co
Packagers
Dosage forms
Form Route Strength
Capsule Oral 100 mg
Capsule Oral 200 mg
Capsule Oral 30 mg
Capsule Oral 300 mg
Injection, solution Parenteral 50 mg/ml
Suspension Oral 125 mg/5 ml
Tablet, chewable Oral 50 mg
Prices
Unit description Cost Unit
Dilantin 125 mg/5ml Suspension 237ml Bottle 69.28 USD bottle
Phenytoin Sodium 50 mg/ml 2.64 USD ml
Phenytek 300 mg capsule 1.47 USD capsule
Phenytoin sod ext 300 mg capsule 1.2 USD capsule
Phenytoin sodium powder 1.16 USD g
Phenytek 200 mg capsule 0.98 USD capsule
Phenytoin 50 mg/ml ampul 0.96 USD ml
Phenytoin sod ext 200 mg capsule 0.8 USD capsule
Phenytoin 50 mg/ml vial 0.67 USD ml
Phenytoin 100 mg/2 ml vial 0.6 USD ml
Dilantin Infatabs 50 mg Chew Tabs 0.6 USD tab
Dilantin 100 mg capsule 0.51 USD capsule
Phenytoin 100 mg/4 ml susp 0.48 USD ml
Dilantin 30 mg capsule 0.46 USD capsule
Phenytoin 250 mg/5 ml vial 0.45 USD ml
Dilantin 50 mg infatab 0.44 USD each
Dilantin 100 mg kapseal 0.39 USD each
Dilantin 30 mg kapseal 0.39 USD each
Phenytoin Sodium Extended 100 mg capsule 0.36 USD capsule
Phenytoin sod ext 100 mg capsule 0.34 USD capsule
Phenytoin powder 0.23 USD g
Phenytoin 125 mg/5ml Suspension 0.15 USD ml
Dilantin Infatabs 50 mg Chewable Tablet 0.08 USD tablet
Dilantin 100 mg Capsule 0.08 USD capsule
Dilantin 30 mg Capsule 0.06 USD capsule
Dilantin-125 25 mg/ml Suspension 0.05 USD ml
Dilantin-30 6 mg/ml Suspension 0.04 USD ml
Taro-Phenytoin 25 mg/ml Suspension 0.03 USD ml
First Prev Next Last
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
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
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00512 Link_out
KEGG Compound C07443 Link_out
PubChem Compound 1775 Link_out
PubChem Substance 46508847 Link_out
ChemSpider 1710 Link_out
ChEBI 8107 Link_out
ChEMBL 8107 Link_out
Therapeutic Targets Database DAP000130 Link_out
PharmGKB PA450947 Link_out
IUPHAR 2624 Link_out
Guide to Pharmacology 2624 Link_out
Drug Product Database 780626 Link_out
RxList http://www.rxlist.com/cgi/generic/phenyt.htm Link_out
Drugs.com http://www.drugs.com/cdi/phenytoin.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/dil1136.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Phenytoin Link_out
ATC Codes
  • N03AB02
  • N03AB04
  • N03AB05
AHFS Codes
  • 28:12.12
PDB Entries Not Available
FDA label Not Available
MSDS show (73.7 KB)
Interactions
Drug Interactions
Drug Interaction
Acenocoumarol Increased hydantoin levels and risk of bleeding
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
Betamethasone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, betamethasone.
Bleomycin The antineoplasic agent decreases the effect of hydantoin
Cabazitaxel Concomitant therapy with a strong CYP3A inducer may decrease concentrations of cabazitaxel. Avoid concomitant therapy.
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
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
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
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.
Phenylbutazone The NSAID, phenylbutazone, may increase the therapeutic and adverse effects of phenytoin.
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.
Rifampin Rifampin may decrease the therapeutic and adverse effects of phenytoin.
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
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.
Vecuronium Phenytoin decreases the effect of the muscle relaxant
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.
Food Interactions
  • 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.
Targets

1. Sodium channel protein type 5 subunit alpha

Pharmacological action: yes
Actions: inhibitor

This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential in the electrocardiogram

Organism class: human
UniProt ID: Q14524 Link_out
Gene: SCN5A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lenkowski PW, Ko SH, Anderson JD, Brown ML, Patel MK: Block of human NaV1.5 sodium channels by novel alpha-hydroxyphenylamide analogues of phenytoin. Eur J Pharm Sci. 2004 Apr;21(5):635-44. Pubmed
  2. Swadron SP, Rudis MI, Azimian K, Beringer P, Fort D, Orlinsky M: A comparison of phenytoin-loading techniques in the emergency department. Acad Emerg Med. 2004 Mar;11(3):244-52. Pubmed

2. Sodium channel protein type 1 subunit alpha

Pharmacological action: yes
Actions: inhibitor

Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient

Organism class: human
UniProt ID: P35498 Link_out
Gene: SCN1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tate SK, Depondt C, Sisodiya SM, Cavalleri GL, Schorge S, Soranzo N, Thom M, Sen A, Shorvon SD, Sander JW, Wood NW, Goldstein DB: Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5507-12. Epub 2005 Apr 1. Pubmed
  2. Tate SK, Singh R, Hung CC, Tai JJ, Depondt C, Cavalleri GL, Sisodiya SM, Goldstein DB, Liou HH: A common polymorphism in the SCN1A gene associates with phenytoin serum levels at maintenance dose. Pharmacogenet Genomics. 2006 Oct;16(10):721-726. Pubmed
  3. Mantegazza M, Curia G, Biagini G, Ragsdale DS, Avoli M: Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders. Lancet Neurol. 2010 Apr;9(4):413-24. Pubmed
Enzymes

1. Cytochrome P450 2C9

Actions: substrate, inhibitor, inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Levy RH: Cytochrome P450 isozymes and antiepileptic drug interactions. Epilepsia. 1995;36 Suppl 5:S8-13. Pubmed
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. Tate SK, Depondt C, Sisodiya SM, Cavalleri GL, Schorge S, Soranzo N, Thom M, Sen A, Shorvon SD, Sander JW, Wood NW, Goldstein DB: Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5507-12. Epub 2005 Apr 1. Pubmed
  5. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  6. Komatsu T, Yamazaki H, Asahi S, Gillam EM, Guengerich FP, Nakajima M, Yokoi T: Formation of a dihydroxy metabolite of phenytoin in human liver microsomes/cytosol: roles of cytochromes P450 2C9, 2C19, and 3A4. Drug Metab Dispos. 2000 Nov;28(11):1361-8. Pubmed

2. Cytochrome P450 2C19

Actions: substrate, inducer

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Levy RH: Cytochrome P450 isozymes and antiepileptic drug interactions. Epilepsia. 1995;36 Suppl 5:S8-13. Pubmed
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  5. Komatsu T, Yamazaki H, Asahi S, Gillam EM, Guengerich FP, Nakajima M, Yokoi T: Formation of a dihydroxy metabolite of phenytoin in human liver microsomes/cytosol: roles of cytochromes P450 2C9, 2C19, and 3A4. Drug Metab Dispos. 2000 Nov;28(11):1361-8. Pubmed
  6. Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. Pubmed

3. Cytochrome P450 2C8

Actions: substrate, inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2B6

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

5. Cytochrome P450 3A4

Actions: substrate, inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2C18

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P33260 Link_out
Gene: CYP2C18 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 3A5

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 3A7

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

9. Cytochrome P450 11B1, mitochondrial

Actions: inhibitor

Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB

UniProt ID: P15538 Link_out
Gene: CYP11B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Solute carrier organic anion transporter family member 1C1

Actions: inhibitor

Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones thyroxine (T4) and rT3. Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol, estrone-3-sulfate and sulfobromophthalein (BSP) are transported with much lower efficiency

UniProt ID: Q9NYB5 Link_out
Gene: SLCO1C1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Westholm DE, Stenehjem DD, Rumbley JN, Drewes LR, Anderson GW: Competitive inhibition of organic anion transporting polypeptide 1c1-mediated thyroxine transport by the fenamate class of nonsteroidal antiinflammatory drugs. Endocrinology. 2009 Feb;150(2):1025-32. Epub 2008 Oct 9. Pubmed
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

2. Multidrug resistance protein 1

Actions: substrate

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Loscher W: Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology. 2007 Feb;52(2):333-46. Epub 2006 Oct 10. Pubmed
  2. Luna-Tortos C, Fedrowitz M, Loscher W: Several major antiepileptic drugs are substrates for human P-glycoprotein. Neuropharmacology. 2008 Dec;55(8):1364-75. Epub 2008 Sep 11. Pubmed

3. Canalicular multispecific organic anion transporter 1

Actions: substrate

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out
Gene: ABCC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Loscher W: Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology. 2007 Feb;52(2):333-46. Epub 2006 Oct 10. Pubmed
Carriers

1. Serum albumin

Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood

UniProt ID: P02768 Link_out
Gene: ALB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen J, Ohnmacht C, Hage DS: Studies of phenytoin binding to human serum albumin by high-performance affinity chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Sep 25;809(1):137-45. Pubmed
  2. Ohnmacht CM, Chen S, Tong Z, Hage DS: Studies by biointeraction chromatography of binding by phenytoin metabolites to human serum albumin. J Chromatogr B Analyt Technol Biomed Life Sci. 2006 May 19;836(1-2):83-91. Epub 2006 Apr 18. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19