Identification

Name
Phenytoin
Accession Number
DB00252  (APRD00241)
Type
Small Molecule
Groups
Approved, Vet 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
Synonyms
  • 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
  • Diphenylhydantoin
  • Fenitoina
  • Phentytoin
  • Phenytoine
  • Phenytoinum
External IDs
NSC-8722
Product Ingredients
IngredientUNIICASInChI Key
Phenytoin sodium4182431BJH630-93-3FJPYVLNWWICYDW-UHFFFAOYSA-M
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DilantinInjection50 mg/1mLParenteralParke Davis Div Of Pfizer Inc2011-12-302012-01-10Us
DilantinCapsule100 mgOralPfizer1951-12-31Not applicableCanada
DilantinCapsule30 mgOralPfizer1951-12-31Not applicableCanada
DilantinInjection50 mg/1mLParenteralParke Davis Div Of Pfizer Inc2011-12-302012-01-10Us
Dilantin InfatabsTablet50 mgOralPfizer1952-12-31Not applicableCanada
Dilantin Inj 50mg/mlLiquid250 mgIntramuscular; IntravenousParke Davis Division, Warner Lambert Canada Inc.1972-12-311996-09-10Canada
Dilantin KapsealsCapsule, extended release30 mg/1OralPARKE-DAVIS2008-09-222008-09-22Us
Dilantin-125Suspension125 mg/5mLOralParke-Davis Div of Pfizer Inc1953-01-06Not applicableUs
Dilantin-125Suspension125 mg/5mLOralPhysicians Total Care, Inc.1953-01-062010-06-30Us
Dilantin-125 SuspensionSuspension125 mgOralPfizer1953-12-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-phenytoin SodiumCapsule100 mgOralApotex Corporation2017-08-16Not applicableCanada
DilantinCapsule, extended release30 mg/1OralAvera McKennan Hospital2015-09-14Not applicableUs69189 374220180907 15195 3k9s2h
DilantinTablet, chewable50 mg/1OralRemedy Repack2010-08-122013-01-30Us
DilantinCapsule, extended release100 mg/1OralCardinal Health1976-08-272018-06-01Us55154 242920180907 15195 hrs0b5
DilantinCapsule, extended release30 mg/1OralRemedy Repack2010-11-302010-12-01Us
DilantinCapsule, extended release30 mg/1OralPhysicians Total Care, Inc.2003-08-19Not applicableUs00071 3740 66 nlmimage10 e815741b
DilantinCapsule, extended release30 mg/1OralParke-Davis Div of Pfizer Inc1976-08-27Not applicableUs0071 374020180814 13942 4l854h
DilantinCapsule, extended release30 mg/1OralKaiser Foundations Hospitals2009-09-20Not applicableUs
DilantinCapsule, extended release30 mg/1OralRemedy Repack2009-12-032011-02-01Us
DilantinCapsule, extended release100 mg/1OralLake Erie Medical Dba Quality Care Produts Llc1976-08-27Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Dilantin W Phenobarbital 15mgPhenytoin sodium (100 mg) + Phenobarbital (15 mg)CapsuleOralParke Davis Division, Warner Lambert Canada Inc.1951-12-311999-04-08Canada
Dilantin W Phenobarbital 30mg CapPhenytoin sodium (100 mg) + Phenobarbital (30 mg)CapsuleOralParke Davis Division, Warner Lambert Canada Inc.1969-12-311997-08-25Canada
International/Other Brands
Epanutin ( Pfizer) / Eptoin
Categories
UNII
6158TKW0C5
CAS number
57-41-0
Weight
Average: 252.268
Monoisotopic: 252.089877638
Chemical Formula
C15H12N2O2
InChI Key
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)
IUPAC Name
5,5-diphenylimidazolidine-2,4-dione
SMILES
O=C1NC(=O)C(N1)(C1=CC=CC=C1)C1=CC=CC=C1

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.

Associated Conditions
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.

TargetActionsOrganism
ASodium channel protein type 5 subunit alpha
inhibitor
Human
ASodium channel protein type 1 subunit alpha
inhibitor
Human
UNuclear receptor subfamily 1 group I member 2Not AvailableHuman
USodium channel subunit beta-1Not AvailableHuman
USodium channel protein type 3 subunit alphaNot AvailableHuman
Absorption

Bioavailability 70-100% oral, 24.4% rectal. 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%. There are reports indicating that a low content of albumin in the body can produce a significant increase in the free phenytoin producing an increase in the frequency and/or potency of side effects such as somnolence, confusion and ataxia.[1]

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)

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
PathwayCategory
Fosphenytoin (Antiarrhythmic) Metabolism PathwayDrug metabolism
Fosphenytoin (Antiarrhythmic) Action PathwayDrug action
Phenytoin (Antiarrhythmic) Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2C9CYP2C9*3(C;C) / (A;C)C AlleleEffect Directly StudiedPatients with this genotype have reduced metabolism of phenytoin.Details
HLA class I histocompatibility antigen, B-15 alpha chainHLA-B*15:02Not AvailableHLA-B*15ADR Directly StudiedThe presence of this genotype in HLA-B is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis when treated with phenytoin.Details
Cytochrome P450 2C19CYP2C19*2ANot Available681G>AADR InferredPoor drug metabolizer, risk of drug toxicity.Details
Cytochrome P450 2C19CYP2C19*2BNot Available681G>AADR InferredPoor drug metabolizer, risk of drug toxicity.Details
Cytochrome P450 2C19CYP2C19*3Not Available636G>AADR InferredPoor drug metabolizer, risk of drug toxicity.Details
Cytochrome P450 2C19CYP2C19*4Not Available1A>GADR InferredPoor drug metabolizer, risk of drug toxicity.Details
Cytochrome P450 2C19CYP2C19*5Not Available1297C>TADR InferredPoor drug metabolizer, risk of drug toxicity.Details
Cytochrome P450 2C19CYP2C19*6Not Available395G>AADR InferredPoor drug metabolizer, risk of drug toxicity.Details
Cytochrome P450 2C19CYP2C19*7Not Available19294T>AADR InferredPoor drug metabolizer, risk of drug toxicity.Details
Cytochrome P450 2C19CYP2C19*22Not Available557G>C / 991A>GADR InferredPoor drug metabolizer, risk of drug toxicity.Details
Cytochrome P450 2C19CYP2C19*24Not Available99C>T / 991A>G  … show all ADR InferredPoor drug metabolizer, risk of drug toxicity.Details
Cytochrome P450 2C19CYP2C19*35Not Available12662A>GADR InferredPoor drug metabolizer, risk of drug toxicity.Details
Cytochrome P450 2C9CYP2C9*2Not Available430C>TADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*3Not Available1075A>CADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*4Not Available1076T>CADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*5Not Available1080C>GADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*8Not Available449G>AADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*11Not Available1003C>TADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*12Not Available1465C>TADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*13Not Available269T>CADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*14Not Available374G>AADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*16Not Available895A>GADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*18Not Available1075A>C / 1190A>C  … show all ADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*26Not Available389C>GADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*28Not Available641A>TADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*30Not Available1429G>AADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*33Not Available395G>AADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*6Not Available818delAADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*15Not Available485C>AADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*25Not Available353_362delAGAAATGGAAADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*35Not Available374G>T / 430C>TADR InferredPoor drug metabolizer, risk of drug toxicity. Consider lower dose.Details
Cytochrome P450 2C9CYP2C9*6Not Available818delAEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*15Not Available485C>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*25Not Available353_362delAGAAATGGAAEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*35Not Available374G>T / 430C>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*2Not Available430C>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*4Not Available1076T>CEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*5Not Available1080C>GEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*8Not Available449G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*11Not Available1003C>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*12Not Available1465C>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*13Not Available269T>CEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*14Not Available374G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*16Not Available895A>GEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*18Not Available1075A>C / 1190A>C  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*26Not Available389C>GEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*28Not Available641A>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*30Not Available1429G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*33Not Available395G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails

Interactions

Drug Interactions
DrugInteraction
(6R)-Folinic acidThe serum concentration of Phenytoin can be decreased when it is combined with (6R)-Folinic acid.
(6S)-5,6,7,8-tetrahydrofolateThe serum concentration of Phenytoin can be decreased when it is combined with (6S)-5,6,7,8-tetrahydrofolate.
(R)-warfarinThe metabolism of Phenytoin can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Phenytoin can be decreased when combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylamphetamineThe therapeutic efficacy of Phenytoin can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe therapeutic efficacy of Phenytoin can be decreased when used in combination with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be decreased when it is combined with Phenytoin.
3,4-MethylenedioxyamphetamineThe therapeutic efficacy of Phenytoin can be decreased when used in combination with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of Phenytoin can be decreased when combined with 3,5-diiodothyropropionic acid.
4-Bromo-2,5-dimethoxyamphetamineThe therapeutic efficacy of Phenytoin can be decreased when used in combination with 4-Bromo-2,5-dimethoxyamphetamine.
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.

References

Synthesis Reference

Mahdi B. Fawzi, Anne K. Taylor, "Parenteral phenytoin preparations." U.S. Patent US4642316, issued April, 1981.

US4642316
General References
  1. Mallet L, Spinewine A, Huang A: The challenge of managing drug interactions in elderly people. Lancet. 2007 Jul 14;370(9582):185-191. doi: 10.1016/S0140-6736(07)61092-7. [PubMed:17630042]
  2. Link [Link]
External Links
Human Metabolome Database
HMDB0014397
KEGG Drug
D00512
KEGG Compound
C07443
PubChem Compound
1775
PubChem Substance
46508847
ChemSpider
1710
BindingDB
50003655
ChEBI
8107
ChEMBL
CHEMBL16
Therapeutic Targets Database
DAP000130
PharmGKB
PA450947
IUPHAR
2624
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Phenytoin
ATC Codes
N03AB02 — PhenytoinN03AB52 — Phenytoin, combinations
AHFS Codes
  • 28:12.12 — Hydantoins
MSDS
Download (73.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedPreventionCognitive Impairments1
0TerminatedPreventionEpilepsies / Traumatic Brain Injury (TBI)1
1CompletedNot AvailableHealthy Volunteers2
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentCocaine-Related Disorders1
1CompletedTreatmentEpilepsies2
1CompletedTreatmentHealthy Participants1
1TerminatedTreatmentEpilepsies1
1, 2CompletedTreatmentChronic Myeloproliferative Disorders / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms / Precancerous Conditions1
2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Lymphoma, Hodgkins / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Lymphoma, Low-Grade / Mantle Cell Lymphoma (MCL) / Small Lymphocytic Lymphoma (SLL) / T-Cell Lymphomas1
2CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Mother to Child Transmission / Pregnancy1
2CompletedTreatmentDisseminated Sclerosis / Optic Neuritis1
2RecruitingTreatmentOptic Neuritis1
2RecruitingTreatmentRe-Epithelialization / Wound site1
2TerminatedTreatmentHaemoglobinopathies congenital / Sickle Cell Disorders / Thalassaemic disorders1
2TerminatedTreatmentNonconvulsive Electrographic Seizures1
2Unknown StatusTreatmentNodding Syndrome1
3CompletedTreatmentCraniocerebral Injuries / Post-Traumatic Seizure Disorder1
3CompletedTreatmentEpilepsies1
3CompletedTreatmentGrand Mal Status Epilepticus / Non-convulsive Status Epilepticus1
3CompletedTreatmentHealthy Volunteers1
3CompletedTreatmentPediatric Status Epilepticus1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
4CompletedOtherCognitive Measures / Driving Simulator Performance1
4CompletedTreatmentBronchial Asthma1
4CompletedTreatmentDepression1
4CompletedTreatmentEpilepsies1
4CompletedTreatmentGrand mal Generalized tonic-clonic seizure1
4CompletedTreatmentSubarachnoid Hemorrhage / Traumatic Brain Injury (TBI)1
4RecruitingTreatmentAcute Kidney Injury (AKI) / Impaired Renal Function / Pharmacokinetics / Renal Failure1
4RecruitingTreatmentEpilepsies1
4TerminatedTreatmentEpilepsies1
4TerminatedTreatmentSeizures1
4Unknown StatusPreventionMeningitis, Pneumococcal / Seizures1
Not AvailableCompletedNot AvailableHealthy Volunteers1
Not AvailableCompletedTreatmentCysticercosis / Epilepsies1
Not AvailableCompletedTreatmentOsteonecrosis Due to Drugs, Jaw1
Not AvailableRecruitingNot AvailableEpilepsies1
Not AvailableRecruitingOtherHealthy Volunteers2
Not AvailableTerminatedPreventionTraumatic Brain Injury (TBI)1
Not AvailableTerminatedTreatmentSubarachnoid Hemorrhage1
Not AvailableUnknown StatusTreatmentImpulsive Aggression / Posttraumatic Stress Disorders1

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
  • Actavis Group
  • Amerisource Health Services Corp.
  • Amneal Pharmaceuticals
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Barr Pharmaceuticals
  • Baxter International Inc.
  • Bilcare Inc.
  • Bryant Ranch Prepack
  • C.O. Truxton Inc.
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Carlisle Laboratories Inc.
  • Comprehensive Consultant Services Inc.
  • Coupler Enterprises Inc.
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • General Injectables and Vaccines Inc.
  • Heartland Repack Services LLC
  • Hikma Pharmaceuticals
  • Hospira Inc.
  • JHP Pharmaceuticals LLC
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Major Pharmaceuticals
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Neuman Distributors Inc.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pfizer Inc.
  • Pharmaceutical Packaging Center
  • Pharmedix
  • Physicians Total Care Inc.
  • Prasco Labs
  • Precision Dose Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • Spectrum Pharmaceuticals
  • Stat Rx Usa
  • Sun Pharmaceutical Industries Ltd.
  • Taro Pharmaceuticals USA
  • Tya Pharmaceuticals
  • UDL Laboratories
  • Vangard Labs Inc.
  • Vistapharm Inc.
  • Warner Chilcott Co. Inc.
  • Warner Lambert Company LLC
  • West-Ward Pharmaceuticals
  • Wockhardt Ltd.
  • Xactdose Inc.
Dosage forms
FormRouteStrength
CapsuleOral30 mg
Capsule, extended releaseOral30 mg/1
InjectionParenteral50 mg/1mL
TabletOral50 mg
Tablet, chewableOral50 mg/1
LiquidIntramuscular; Intravenous250 mg
CapsuleOral
SuspensionOral125 mg
SuspensionOral30 mg
CapsuleOral100 mg
Capsule, extended releaseOral300 mg/1
SuspensionOral100 mg/4mL
SuspensionOral125 mg/5mL
CapsuleOral100 mg/1
Capsule, extended releaseOral100 mg/1
Capsule, extended releaseOral200 mg/1
InjectionIntramuscular; Intravenous250 mg/5mL
InjectionIntramuscular; Intravenous50 mg/1mL
InjectionIntravenous50 mg/1mL
Injection, solutionIntramuscular; Intravenous50 mg/1mL
LiquidIntramuscular; Intravenous50 mg
SolutionIntramuscular; Intravenous50 mg
Prices
Unit descriptionCostUnit
Dilantin 125 mg/5ml Suspension 237ml Bottle69.28USD bottle
Phenytoin Sodium 50 mg/ml2.64USD ml
Phenytek 300 mg capsule1.47USD capsule
Phenytoin sod ext 300 mg capsule1.2USD capsule
Phenytoin sodium powder1.16USD g
Phenytek 200 mg capsule0.98USD capsule
Phenytoin 50 mg/ml ampul0.96USD ml
Phenytoin sod ext 200 mg capsule0.8USD capsule
Phenytoin 50 mg/ml vial0.67USD ml
Phenytoin 100 mg/2 ml vial0.6USD ml
Dilantin Infatabs 50 mg Chew Tabs0.6USD tab
Dilantin 100 mg capsule0.51USD capsule
Phenytoin 100 mg/4 ml susp0.48USD ml
Dilantin 30 mg capsule0.46USD capsule
Phenytoin 250 mg/5 ml vial0.45USD ml
Dilantin 50 mg infatab0.44USD each
Dilantin 100 mg kapseal0.39USD each
Dilantin 30 mg kapseal0.39USD each
Phenytoin Sodium Extended 100 mg capsule0.36USD capsule
Phenytoin sod ext 100 mg capsule0.34USD capsule
Phenytoin powder0.23USD g
Phenytoin 125 mg/5ml Suspension0.15USD ml
Dilantin Infatabs 50 mg Chewable Tablet0.08USD tablet
Dilantin 100 mg Capsule0.08USD capsule
Dilantin 30 mg Capsule0.06USD capsule
Dilantin-125 25 mg/ml Suspension0.05USD ml
Dilantin-30 6 mg/ml Suspension0.04USD ml
Taro-Phenytoin 25 mg/ml Suspension0.03USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)286 °CPhysProp
water solubility32 mg/L (at 22 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.47HANSCH,C ET AL. (1995)
Caco2 permeability-4.57ADME Research, USCD
pKa8.33SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0711 mg/mLALOGPS
logP2.26ALOGPS
logP2.15ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)9.47ChemAxon
pKa (Strongest Basic)-9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.2 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity70.18 m3·mol-1ChemAxon
Polarizability25.48 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9909
Blood Brain Barrier+0.976
Caco-2 permeable+0.8867
P-glycoprotein substrateNon-substrate0.5593
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.987
Renal organic cation transporterNon-inhibitor0.8995
CYP450 2C9 substrateNon-substrate0.733
CYP450 2D6 substrateSubstrate0.8911
CYP450 3A4 substrateNon-substrate0.7591
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.8304
CYP450 2D6 inhibitorNon-inhibitor0.935
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8994
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.855
BiodegradationNot ready biodegradable0.992
Rat acute toxicity2.1567 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9793
hERG inhibition (predictor II)Non-inhibitor0.8916
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (9.46 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-003r-7930000000-447969b9c242748dd943
GC-MS Spectrum - CI-BGC-MSsplash10-0udi-0090000000-4176043a7a73caee2667
GC-MS Spectrum - EI-BGC-MSsplash10-0zgi-5960000000-e1dcb47a1c082f04f456
GC-MS Spectrum - CI-BGC-MSsplash10-0udi-1390000000-22c71a7e4dbf9c7acab5
GC-MS Spectrum - CI-BGC-MSsplash10-0udi-2190000000-50174e33af92b04d1a6e
Mass Spectrum (Electron Ionization)MSsplash10-0f89-4940000000-2a0dda513d9f63dc6610
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0090000000-aaae845342f345f89695
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0390000000-f8da1896c569c120faa2
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0920000000-07c872b05aade63c402b
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0900000000-be6790637be99260525e
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0900000000-9a17fa0b243c8282f3ba
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0900000000-69302626996b2b24c153
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0fai-0690000000-f9eeceb82d117127f6ea
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0910000000-9edcfc62014a6aa7778f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0900000000-d4dde5db680fb7722a49
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0ue9-0900000000-482874b33812389ae726
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0900000000-44f07dc29daf8cdf80c2
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-1900000000-1241292d531ed37544c7
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-0950000000-a80521d4dc3976a29b2c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0ue9-2900000000-a58471ae75fa7319c03d
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylhydantoins. These are heterocyclic aromatic compounds containing an imiazolidinedione moiety substituted by a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azolidines
Sub Class
Imidazolidines
Direct Parent
Phenylhydantoins
Alternative Parents
Diphenylmethanes / Phenylimidazolidines / Alpha amino acids and derivatives / 5-monosubstituted hydantoins / N-acyl ureas / Dicarboximides / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides
show 2 more
Substituents
Diphenylmethane / 5-phenylhydantoin / Phenylimidazolidine / Alpha-amino acid or derivatives / 5-monosubstituted hydantoin / N-acyl urea / Ureide / Monocyclic benzene moiety / Benzenoid / Dicarboximide
show 13 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazolidine-2,4-dione (CHEBI:8107)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function
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 pr...
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
Molecular Weight
226937.475 Da
References
  1. Mitiushin VM, Kozyreva EV: [Several types of mitochondrial ultrastructure in animal cell mitochondria and their relationship to energy production]. Tsitologiia. 1978 Apr;20(4):371-9. [PubMed:150666]
  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:15001403]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity
Specific Function
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...
Gene Name
SCN1A
Uniprot ID
P35498
Uniprot Name
Sodium channel protein type 1 subunit alpha
Molecular Weight
228969.49 Da
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:15805193]
  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):721-6. [PubMed:17001291]
  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. doi: 10.1016/S1474-4422(10)70059-4. [PubMed:20298965]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Curator comments
weak activator
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Faucette SR, Wang H, Hamilton GA, Jolley SL, Gilbert D, Lindley C, Yan B, Negishi M, LeCluyse EL: Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers. Drug Metab Dispos. 2004 Mar;32(3):348-58. [PubMed:14977870]
  2. Kobayashi K, Yamagami S, Higuchi T, Hosokawa M, Chiba K: Key structural features of ligands for activation of human pregnane X receptor. Drug Metab Dispos. 2004 Apr;32(4):468-72. [PubMed:15039302]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Voltage-gated sodium channel activity involved in purkinje myocyte action potential
Specific Function
Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-1 can modulate multiple alpha subunit isoforms from brain, skele...
Gene Name
SCN1B
Uniprot ID
Q07699
Uniprot Name
Sodium channel subunit beta-1
Molecular Weight
24706.955 Da
References
  1. Lucas PT, Meadows LS, Nicholls J, Ragsdale DS: An epilepsy mutation in the beta1 subunit of the voltage-gated sodium channel results in reduced channel sensitivity to phenytoin. Epilepsy Res. 2005 May;64(3):77-84. [PubMed:15922564]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Voltage-gated sodium channel activity
Specific Function
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...
Gene Name
SCN3A
Uniprot ID
Q9NY46
Uniprot Name
Sodium channel protein type 3 subunit alpha
Molecular Weight
226291.905 Da
References
  1. Lucas PT, Meadows LS, Nicholls J, Ragsdale DS: An epilepsy mutation in the beta1 subunit of the voltage-gated sodium channel results in reduced channel sensitivity to phenytoin. Epilepsy Res. 2005 May;64(3):77-84. [PubMed:15922564]

Enzymes

Details
1. Cytochrome P450 2C9
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Steroid hydroxylase activity
Specific Function
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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Levy RH: Cytochrome P450 isozymes and antiepileptic drug interactions. Epilepsia. 1995;36 Suppl 5:S8-13. [PubMed:8806399]
  2. 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:15805193]
  3. 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:11038165]
  4. Lynch T, Price A: The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician. 2007 Aug 1;76(3):391-6. [PubMed:17708140]
  5. van der Weide J, Steijns LS, van Weelden MJ, de Haan K: The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement. Pharmacogenetics. 2001 Jun;11(4):287-91. [PubMed:11434505]
  6. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  7. Get to Know an Enzyme: CYP2C9 [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Levy RH: Cytochrome P450 isozymes and antiepileptic drug interactions. Epilepsia. 1995;36 Suppl 5:S8-13. [PubMed:8806399]
  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:19515014]
  3. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  4. 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:11038165]
  5. Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. [PubMed:9014207]
  6. Giancarlo GM, Venkatakrishnan K, Granda BW, von Moltke LL, Greenblatt DJ: Relative contributions of CYP2C9 and 2C19 to phenytoin 4-hydroxylation in vitro: inhibition by sulfaphenazole, omeprazole, and ticlopidine. Eur J Clin Pharmacol. 2001 Apr;57(1):31-6. [PubMed:11372587]
  7. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  8. Cytochrome P450 2C19 by Straight Healthcare [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Steroid hydroxylase activity
Specific Function
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 un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  2. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
  3. Ferguson SS, Chen Y, LeCluyse EL, Negishi M, Goldstein JA: Human CYP2C8 is transcriptionally regulated by the nuclear receptors constitutive androstane receptor, pregnane X receptor, glucocorticoid receptor, and hepatic nuclear factor 4alpha. Mol Pharmacol. 2005 Sep;68(3):747-57. Epub 2005 Jun 2. [PubMed:15933212]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
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 un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Ohno Y, Hisaka A, Ueno M, Suzuki H: General framework for the prediction of oral drug interactions caused by CYP3A4 induction from in vivo information. Clin Pharmacokinet. 2008;47(10):669-80. doi: 10.2165/00003088-200847100-00004. [PubMed:18783297]
  3. Zhou SF: Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr Drug Metab. 2008 May;9(4):310-22. [PubMed:18473749]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
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 un...
Gene Name
CYP2C18
Uniprot ID
P33260
Uniprot Name
Cytochrome P450 2C18
Molecular Weight
55710.075 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inducer
General Function
Oxygen binding
Specific Function
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Usui T, Saitoh Y, Komada F: Induction of CYP3As in HepG2 cells by several drugs. Association between induction of CYP3A4 and expression of glucocorticoid receptor. Biol Pharm Bull. 2003 Apr;26(4):510-7. [PubMed:12673034]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxygen binding
Specific Function
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 un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Usui T, Saitoh Y, Komada F: Induction of CYP3As in HepG2 cells by several drugs. Association between induction of CYP3A4 and expression of glucocorticoid receptor. Biol Pharm Bull. 2003 Apr;26(4):510-7. [PubMed:12673034]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 11-beta-monooxygenase activity
Specific Function
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 cytochro...
Gene Name
CYP11B1
Uniprot ID
P15538
Uniprot Name
Cytochrome P450 11B1, mitochondrial
Molecular Weight
57572.44 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inducer
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Interactions [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 3 lacks trans...
Gene Name
UGT1A6
Uniprot ID
P19224
Uniprot Name
UDP-glucuronosyltransferase 1-6
Molecular Weight
60750.215 Da
References
  1. Kostrubsky SE, Sinclair JF, Strom SC, Wood S, Urda E, Stolz DB, Wen YH, Kulkarni S, Mutlib A: Phenobarbital and phenytoin increased acetaminophen hepatotoxicity due to inhibition of UDP-glucuronosyltransferases in cultured human hepatocytes. Toxicol Sci. 2005 Sep;87(1):146-55. doi: 10.1093/toxsci/kfi211. Epub 2005 Jun 2. [PubMed:15933229]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Kostrubsky SE, Sinclair JF, Strom SC, Wood S, Urda E, Stolz DB, Wen YH, Kulkarni S, Mutlib A: Phenobarbital and phenytoin increased acetaminophen hepatotoxicity due to inhibition of UDP-glucuronosyltransferases in cultured human hepatocytes. Toxicol Sci. 2005 Sep;87(1):146-55. doi: 10.1093/toxsci/kfi211. Epub 2005 Jun 2. [PubMed:15933229]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Murphy A, Wilbur K: Phenytoin-diazepam interaction. Ann Pharmacother. 2003 May;37(5):659-63. doi: 10.1345/aph.1C413. [PubMed:12708941]
  2. Gryn SE, Teft WA, Kim RB: Profound reduction in the tamoxifen active metabolite endoxifen in a patient on phenytoin for epilepsy compared with a CYP2D6 genotype matched cohort. Pharmacogenet Genomics. 2014 Jul;24(7):367-9. doi: 10.1097/FPC.0000000000000051. [PubMed:24915025]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
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 colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
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:15282104]
  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:16621742]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Thyroid hormone transmembrane transporter activity
Specific Function
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-gluc...
Gene Name
SLCO1C1
Uniprot ID
Q9NYB5
Uniprot Name
Solute carrier organic anion transporter family member 1C1
Molecular Weight
78695.625 Da
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. doi: 10.1210/en.2008-0188. Epub 2008 Oct 9. [PubMed:18845642]
  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:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
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:17045309]
  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. doi: 10.1016/j.neuropharm.2008.08.032. Epub 2008 Sep 11. [PubMed:18824002]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
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:17045309]

Drug created on June 13, 2005 07:24 / Updated on December 09, 2018 01:03