NAV

Fosphenytoin

Identification

Summary

Fosphenytoin is an antiepileptic agent used for the management of generalized convulsive status epilepticus and prevention and treatment of seizures occurring during neurosurgery.

Brand Names
Cerebyx
Generic Name
Fosphenytoin
DrugBank Accession Number
DB01320
Background

Fosphenytoin is a water-soluble phenytoin prodrug used only in hospitals for the treatment of epileptic seizures. It works by slowing down impulses in the brain that cause seizures. Its main mechanism is to block frequency-dependent, use-dependent and voltage-dependent neuronal sodium channels, and therefore limit repetitive firing of action potentials.

Type
Small Molecule
Groups
Approved, Investigational
Structure
3D
Similar Structures
Weight
Average: 362.2739
Monoisotopic: 362.066772734
Chemical Formula
C16H15N2O6P
Synonyms
  • (3-Phosphoryloxymethyl)phenytoin
  • Fosfenitoina
  • Fosphenytoin
  • Fosphenytoine
  • Fosphenytoinum
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Pharmacology

Indication

Fosphenytoin is indicated for the treatment of generalized tonic-clonic status epilepticus and for the prevention and treatment of seizures occurring during neurosurgery in adult patients. It can also be substituted, short-term, for oral phenytoin in patients aged two years and older when oral phenytoin administration is not possible.6

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Maintenance ofOral phenytoin treatment•••••••••••••••••••••• •••••••••• ••••••••
Prophylaxis ofSeizures••••••••••••••••••••••••••• •••••••••• ••••••••
Management ofSeizures••••••••••••••••••••••••••• •••••••••• ••••••••
Treatment ofStatus epilepticus••••••••••••••••••••••••••• •••••••••• ••••••••
Treatment ofGeneralized tonic-clonic status epilepticus••••••••••••••••••••••••••• •••••••••• ••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Fosphenytoin is a water-soluble phenytoin prodrug used for the treatment of epileptic seizures. Following parenteral administration of fosphenytoin, fosphenytoin is converted to the anticonvulsant phenytoin by endogenous phosphatases. Each 1.5 mg of fosphenytoin sodium is equivalent to 1.0mg of phenytoin sodium (PE equivalents); care should be taken to calculate the dose required in PE equivalents properly. Serious adverse effects such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN), and hematopoietic complications may occur and indicate an alternate antiepileptic should be used. Withdrawal of fosphenytoin sodium may precipitate seizures and should be done gradually.6

Mechanism of action

Fosphenytoin is a prodrug of phenytoin and accordingly, its anticonvulsant effects are attributable to phenytoin. 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
Humans
Absorption

Fosphenytoin at 15 to 20 mg PE/kg infused at 100 to 150 mg PE/min intravenously yields free plasma phenytoin concentrations similar to an equivalent dose of phenytoin sodium administered at 50 mg/min. Single intravenous administration of fosphenytoin shows a linear increase in mean maximum total phenytoin concentration while the mean maximum unbound phenytoin concentrations increase with both dose and infusion rate. Fosphenytoin is rapidly converted to phenytoin following intravenous administration with a half-life of 15 minutes; if administered intramuscularly, the peak plasma phenytoin concentration is not reached until three hours.6

Volume of distribution

The volume of distribution of fosphenytoin increases with dose and rate, ranging between 4.3 and 10.8 L.6

Protein binding

Fosphenytoin is extensively bound (95-99%) to human plasma proteins, primarily albumin, and displays saturable binding kinetics over a physiologically relevant range of fosphenytoin concentrations. Like fosphenytoin, phenytoin is extensively bound, again mainly to albumin, but can be displaced by fosphenytoin itself. Phenytoin is typically about 88% bound in the absence of fosphenytoin, but this drops to around 60% 0.5-1 hour following fosphenytoin infusion while fosphenytoin is being converted to phenytoin.6

Metabolism

Fosphenytoin is metabolized, likely by phosphatases, to phenytoin, phosphate, and formaldehyde; the formaldehyde is subsequently converted into formate. The phenytoin produced is metabolized hepatically by CYP2C9 and, to a lesser extent, by CYP2C19.6

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Route of elimination

Phenytoin derived from fosphenytoin administration is excreted in the urine primarily as 5-(p-hydroxyphenyl)-5-phenylhydantoin and its glucuronide. There is little unchanged phenytoin (1%–5% of the administered dose), and essentially no fosphenytoin recovered in urine.6

Half-life

Fosphenytoin has a conversion half-life of approximately 15 minutes. The resulting phenytoin has a wide range of mean total half-life values (12 to 28.9 hours), with longer half-life times at higher administered doses.6

Clearance

Not Available

Adverse Effects
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Toxicity

Nausea, vomiting, lethargy, tachycardia, bradycardia, asystole, cardiac arrest, hypotension, syncope, hypocalcemia, metabolic acidosis, and death have been reported in cases of overdosage with fosphenytoin. The median lethal dose of fosphenytoin given intravenously in mice and rats was 156 mg PE/kg and approximately 250 mg PE/kg, or about 0.6 and 2 times, respectively, the maximum human loading dose on a mg/m2 basis. Signs of acute toxicity in animals included ataxia, labored breathing, ptosis, and hypoactivity.

Pathways
PathwayCategory
Fosphenytoin (Antiarrhythmic) Action PathwayDrug action
Fosphenytoin (Antiarrhythmic) Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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interactions in your software
1,2-BenzodiazepineThe metabolism of 1,2-Benzodiazepine can be increased when combined with Fosphenytoin.
AbametapirThe serum concentration of Fosphenytoin can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Fosphenytoin can be increased when combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Fosphenytoin.
AbirateroneThe metabolism of Abiraterone can be increased when combined with Fosphenytoin.
Food Interactions
  • Avoid alcohol. Acute alcohol consumption may increase phenytoin serum concentration, but chronic alcohol use may reduce phenytoin serum concentration.
  • Avoid St. John's Wort. This herb may reduce the serum concentration of phenytoin.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Fosphenytoin sodium7VLR55452Z92134-98-0GQPXYJNXTAFDLT-UHFFFAOYSA-L
Active Moieties
NameKindUNIICASInChI Key
Phenytoinprodrug6158TKW0C557-41-0CXOFVDLJLONNDW-UHFFFAOYSA-N
International/Other Brands
Prodilantin / Sesquient
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CerebyxSolution75 mg / mLIntramuscular; IntravenousSearchlight Pharma Inc2000-03-01Not applicableCanada flag
CerebyxInjection, solution50 mg/1mLIntramuscular; IntravenousPfizer Laboratories Div Pfizer Inc2013-10-28Not applicableUS flag
CerebyxInjection, solution50 mg/1mLIntramuscular; IntravenousParke Davis Div Of Pfizer Inc1996-08-052010-01-01US flag
CerebyxInjection, solution50 mg/1mLIntramuscular; IntravenousPfizer Laboratories Div Pfizer Inc2013-10-28Not applicableUS flag
CerebyxInjection, solution50 mg/1mLIntramuscular; IntravenousParke Davis Div Of Pfizer Inc1996-08-052010-01-01US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FosphenytoinInjection, solution50 mg/1mLIntramuscular; IntravenousFresenius Kabi USA, LLC2009-12-14Not applicableUS flag
Fosphenytoin SodiumInjection, solution50 mg/1mLIntramuscular; IntravenousHospira, Inc.2008-08-252011-11-01US flag
Fosphenytoin SodiumInjection, solution50 mg/1mLIntramuscular; IntravenousWest-Ward Pharmaceuticals Corp2009-12-02Not applicableUS flag
Fosphenytoin sodiumInjection, solution50 mg/1mLIntramuscular; IntravenousGlenmark Pharmaceuticals Inc., USA2023-10-13Not applicableUS flag
Fosphenytoin SodiumInjection, solution50 mg/1mLIntramuscular; IntravenousSun Pharma Global FZE2009-08-142017-01-23US flag

Categories

ATC Codes
N03AB05 — Fosphenytoin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Alpha amino acids and derivatives / N-acyl ureas / Monoalkyl phosphates / Imidazolinones / Isoureas / Propargyl-type 1,3-dipolar organic compounds / Carboximidamides / Azacyclic compounds / Organopnictogen compounds / Organic oxides
show 2 more
Substituents
2-imidazoline / Alkyl phosphate / Alpha-amino acid or derivatives / Aromatic heteromonocyclic compound / Azacycle / Carbonyl group / Carboximidamide / Carboxylic acid derivative / Diphenylmethane / Hydrocarbon derivative
show 16 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazolidine-2,4-dione (CHEBI:5165)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
B4SF212641
CAS number
93390-81-9
InChI Key
XWLUWCNOOVRFPX-UHFFFAOYSA-N
InChI
InChI=1S/C16H15N2O6P/c19-14-16(12-7-3-1-4-8-12,13-9-5-2-6-10-13)17-15(20)18(14)11-24-25(21,22)23/h1-10H,11H2,(H,17,20)(H2,21,22,23)
IUPAC Name
[(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)methoxy]phosphonic acid
SMILES
OP(O)(=O)OCN1C(=O)NC(C1=O)(C1=CC=CC=C1)C1=CC=CC=C1

References

Synthesis Reference

Volker Kirsch, "Process for the preparation of sodium fosphenytoin." U.S. Patent US20050272706, issued December 08, 2005.

US20050272706
General References
  1. Johnson J, Wrenn K: Inappropriate fosphenytoin use in the ED. Am J Emerg Med. 2001 Jul;19(4):293-4. [Article]
  2. Applebaum J, Levine J, Belmaker RH: Intravenous fosphenytoin in acute mania. J Clin Psychiatry. 2003 Apr;64(4):408-9. [Article]
  3. McCleane GJ: Intravenous infusion of fosphenytoin produces prolonged pain relief: a case report. J Pain. 2002 Apr;3(2):156-8. [Article]
  4. Browne TR, Kugler AR, Eldon MA: Pharmacology and pharmacokinetics of fosphenytoin. Neurology. 1996 Jun;46(6 Suppl 1):S3-7. [Article]
  5. Luszczki JJ: Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions. Pharmacol Rep. 2009 Mar-Apr;61(2):197-216. [Article]
  6. FDA Approved Drug Products: SESQUIENT (fosphenytoin) injection [Link]
Human Metabolome Database
HMDB0015417
KEGG Drug
D07993
KEGG Compound
C07840
PubChem Compound
56339
PubChem Substance
46505168
ChemSpider
50839
RxNav
72236
ChEBI
5165
ChEMBL
CHEMBL1201336
ZINC
ZINC000001530922
Therapeutic Targets Database
DAP000520
PharmGKB
PA164746820
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Fosphenytoin
FDA label
Download (820 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
4CompletedTreatmentGeneralized Tonic-Clonic Seizures1
3CompletedTreatmentBenzodiazepine Refractory Status Epilepticus1
3CompletedTreatmentEpilepsy1
3CompletedTreatmentEpilepsy / Status Epilepticus1
2CompletedTreatmentNonconvulsive Seizures1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Akorn Inc.
  • Apotex Inc.
  • APP Pharmaceuticals
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Generamedix Inc.
  • Hikma Pharmaceuticals
  • Hospira Inc.
  • Pfizer Inc.
  • Pharmaforce Inc.
  • Strides Arcolab Limited
  • Sun Pharmaceutical Industries Ltd.
  • Teva Pharmaceutical Industries Ltd.
  • West-Ward Pharmaceuticals
  • Wockhardt Ltd.
Dosage Forms
FormRouteStrength
SolutionIntramuscular; Intravenous75 mg / mL
InjectionIntramuscular; Intravenous50 mg/1mL
InjectionIntravenous50 mg/1mL
Injection, solutionIntramuscular; Intravascular50 mg/1mL
Injection, solutionIntramuscular; Intravenous50 mg/1mL
Injection, solutionIntramuscular; Intravenous75 mg/1mL
Injection, solutionIntravenous100 mg/2mL
Injection, solutionIntravenous500 mg/10mL
SolutionIntramuscular; Intravenous75 mg/1ml
Prices
Unit descriptionCostUnit
Cerebyx 500 mg pe/10 ml vial8.63USD ml
Fosphenytoin 500 mg pe/10 ml0.61USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7635773No2009-12-222029-03-13US flag
US8410077No2013-04-022029-03-13US flag
US9200088No2015-12-012029-03-13US flag
US9493582No2016-11-152033-02-27US flag
US9750822No2017-09-052029-03-13US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.145 mg/mLALOGPS
logP1.08ALOGPS
logP1.67Chemaxon
logS-3.4ALOGPS
pKa (Strongest Acidic)1.46Chemaxon
pKa (Strongest Basic)-9.7Chemaxon
Physiological Charge-2Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area116.17 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity87.05 m3·mol-1Chemaxon
Polarizability33.23 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.5244
Blood Brain Barrier+0.9215
Caco-2 permeable-0.639
P-glycoprotein substrateSubstrate0.5
P-glycoprotein inhibitor INon-inhibitor0.7952
P-glycoprotein inhibitor IINon-inhibitor0.8466
Renal organic cation transporterNon-inhibitor0.8731
CYP450 2C9 substrateNon-substrate0.7094
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6873
CYP450 1A2 substrateNon-inhibitor0.8477
CYP450 2C9 inhibitorNon-inhibitor0.7802
CYP450 2D6 inhibitorNon-inhibitor0.8859
CYP450 2C19 inhibitorNon-inhibitor0.7169
CYP450 3A4 inhibitorNon-inhibitor0.7672
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9083
Ames testNon AMES toxic0.614
CarcinogenicityNon-carcinogens0.7835
BiodegradationNot ready biodegradable0.9674
Rat acute toxicity2.4215 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9578
hERG inhibition (predictor II)Non-inhibitor0.7299
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-00ls-4941000000-7f020f5c4237af5bfb3c
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0049000000-938f80f51b0b80575b74
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-1009000000-dfe901a1fa3f538f80fb
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0091000000-1cb1661bc3bc3150fab3
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-2129000000-7c904411cf5c76fd8abc
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-3901000000-ba2ddf868cd406d5df72
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-016r-5692000000-b3325120dc7c54b937e4
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-194.786207
predicted
DarkChem Lite v0.1.0
[M-H]-166.04485
predicted
DeepCCS 1.0 (2019)
[M+H]+194.685707
predicted
DarkChem Lite v0.1.0
[M+H]+168.40283
predicted
DeepCCS 1.0 (2019)
[M+Na]+193.591907
predicted
DarkChem Lite v0.1.0
[M+Na]+174.49599
predicted
DeepCCS 1.0 (2019)

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
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Details1. Sodium channel protein type 5 subunit alpha
Kind
Protein
Organism
Humans
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. 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. [Article]
  2. 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. [Article]
  3. 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. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Enzymes

Details1. Cytochrome P450 1A2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Johannessen SI, Landmark CJ: Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol. 2010 Sep;8(3):254-67. doi: 10.2174/157015910792246254. [Article]
  2. Clark SL, Leloux MR, Dierkhising RA, Cascino GD, Hocker SE: IV fosphenytoin in obese patients: Dosing strategies, safety, and efficacy. Neurol Clin Pract. 2017 Feb;7(1):45-52. doi: 10.1212/CPJ.0000000000000322. [Article]
  3. Fosphenytoin sodium - Drug Summary - Prescribers Digital Reference - Drug Interactions [Link]
Details2. UDP-glucuronosyltransferase 1-6
Kind
Protein
Organism
Humans
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. [Article]
Details3. UDP-glucuronosyltransferase 1-9
Kind
Protein
Organism
Humans
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. [Article]
Details4. Cytochrome P450 2C19
Kind
Protein
Organism
Humans
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. Anderson GD: Pharmacokinetic, pharmacodynamic, and pharmacogenetic targeted therapy of antiepileptic drugs. Ther Drug Monit. 2008 Apr;30(2):173-80. doi: 10.1097/FTD.0b013e318167d11b. [Article]
  2. Hennessy S, Leonard CE, Freeman CP, Metlay JP, Chu X, Strom BL, Bilker WB: CYP2C9, CYP2C19, and ABCB1 genotype and hospitalization for phenytoin toxicity. J Clin Pharmacol. 2009 Dec;49(12):1483-7. doi: 10.1177/0091270009343006. Epub 2009 Jul 17. [Article]
  3. Klotz U: The role of pharmacogenetics in the metabolism of antiepileptic drugs: pharmacokinetic and therapeutic implications. Clin Pharmacokinet. 2007;46(4):271-9. [Article]
  4. Rosemary J, Surendiran A, Rajan S, Shashindran CH, Adithan C: Influence of the CYP2C9 AND CYP2C19 polymorphisms on phenytoin hydroxylation in healthy individuals from south India. Indian J Med Res. 2006 May;123(5):665-70. [Article]
Details5. Cytochrome P450 2B6
Kind
Protein
Organism
Humans
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. Wang H, Faucette S, Moore R, Sueyoshi T, Negishi M, LeCluyse E: Human constitutive androstane receptor mediates induction of CYP2B6 gene expression by phenytoin. J Biol Chem. 2004 Jul 9;279(28):29295-301. Epub 2004 Apr 28. [Article]
  2. 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. [Article]
Details6. Cytochrome P450 2C9
Kind
Protein
Organism
Humans
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
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Sahi J, Shord SS, Lindley C, Ferguson S, LeCluyse EL: Regulation of cytochrome P450 2C9 expression in primary cultures of human hepatocytes. J Biochem Mol Toxicol. 2009 Jan-Feb;23(1):43-58. doi: 10.1002/jbt.20264. [Article]
  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. [Article]
  3. Goldstein JA: Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Br J Clin Pharmacol. 2001 Oct;52(4):349-55. [Article]
  4. Klotz U: The role of pharmacogenetics in the metabolism of antiepileptic drugs: pharmacokinetic and therapeutic implications. Clin Pharmacokinet. 2007;46(4):271-9. [Article]
  5. Kim KA, Park JY: Inhibitory effect of glyburide on human cytochrome p450 isoforms in human liver microsomes. Drug Metab Dispos. 2003 Sep;31(9):1090-2. [Article]
  6. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Details7. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
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. Zhou SF: Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr Drug Metab. 2008 May;9(4):310-22. [Article]
  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. [Article]
  3. McDonnell AM, Dang CH: Basic review of the cytochrome p450 system. J Adv Pract Oncol. 2013 Jul;4(4):263-8. [Article]
  4. Fan HC, Lee HS, Chang KP, Lee YY, Lai HC, Hung PL, Lee HF, Chi CS: The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism. Int J Mol Sci. 2016 Aug 1;17(8). pii: ijms17081242. doi: 10.3390/ijms17081242. [Article]

Carriers

Details1. Serum albumin
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Other/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. Walker MC, Patsalos PN: Clinical pharmacokinetics of new antiepileptic drugs. Pharmacol Ther. 1995;67(3):351-84. [Article]
Details2. Thyroxine-binding globulin
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Major thyroid hormone transport protein in serum.
Gene Name
SERPINA7
Uniprot ID
P05543
Uniprot Name
Thyroxine-binding globulin
Molecular Weight
46324.12 Da
References
  1. CYTOMEL (liothyronine) FDA label [File]

Drug created at June 30, 2007 17:18 / Updated at January 02, 2024 23:50