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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2022-03-07 02:51:58 UTC
HMDB IDHMDB0015417
Secondary Accession Numbers
  • HMDB15417
Metabolite Identification
Common NameFosphenytoin
DescriptionFosphenytoin, also known as cerebyx or HMPDP, belongs to the class of organic compounds known as diphenylmethanes. Diphenylmethanes are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups. Fosphenytoin is a drug which is used for the control of generalized convulsive status epilepticus and prevention and treatment of seizures occurring during neurosurgery. it can also be substituted, short-term, for oral phenytoin. Fosphenytoin can cause hyperphosphatemia in end-stage renal failure patients. Fosphenytoin is an extremely weak basic (essentially neutral) compound (based on its pKa). In humans, fosphenytoin is involved in the metabolic disorder called the fosphenytoin (antiarrhythmic) metabolism pathway. Fosphenytoin is a potentially toxic compound. Fosphenytoin is approved in the United States for the short term (five days or fewer) treatment of epilepsy when more widely used means of phenytoin administration are not possible or are ill-advised, such as endotracheal intubation, status epilepticus or some other type of repeated seizures; vomiting, and/or the patient is unalert or not awake or both. One solution was to develop a prodrug that did not have these drawbacks. Fosphenytoin (fosphenytoin sodium, trade names Cerebyx, Parke-Davis; Prodilantin, Pfizer Holding France) is a water-soluble phenytoin prodrug that is administered intravenously to deliver phenytoin, potentially more safely than intravenous phenytoin. Side effects are similar to intravenous phenytoin and include hypotension, cardiac arrhythmias, CNS adverse events (nystagmus, dizziness, sedation/somnolence, ataxia and stupor), and local dermatological reactions. Purple glove syndrome probably occurs with fosphenytoin but possibly at lower frequency than with intravenous phenytoin. It is most commonly used in the acute treatment of convulsive status epilepticus. On 18 November 2004, Sicor (a subsidiary of Teva) received a tentative approval letter from the United States Food and Drug Administration for a generic version of fosphenytoin. One millimole of phenytoin is produced for every millimole of fosphenytoin administered; the hydrolysis of fosphenytoin also yields phosphate and formaldehyde, the latter of which is subsequently metabolized to formate, which is in turn metabolized by a folate dependent mechanism. Fosphenytoin was approved by the Food and Drug Administration (FDA) on August 5, 1996 for use in epilepsy. Simply putting patients on other drugs is not always an option; this was especially true before 1993, when the number of anticonvulsants available was much more limited. In 2003, it was reported that even though anticonvulsants are often very effective in mania, and acute mania requires rapid treatment, fosphenytoin had no antimanic effect.
Structure
Data?1582753294
Synonyms
ValueSource
(3-Phosphoryloxymethyl)phenytoinHMDB
CerebyxHMDB
HMPDPHMDB
3-(Hydroxymethyl)phenytoin disodium phosphateHMDB
Fosphenytoin, disodium saltHMDB
ProdilantinHMDB
Fosphenytoin sodiumHMDB
3-(Hydroxymethyl)phenytoin phosphate esterHMDB
Chemical FormulaC16H15N2O6P
Average Molecular Weight362.2739
Monoisotopic Molecular Weight362.066772734
IUPAC Name[(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)methoxy]phosphonic acid
Traditional Namefosphenytoin
CAS Registry Number93390-81-9
SMILES
OP(O)(=O)OCN1C(=O)NC(C1=O)(C1=CC=CC=C1)C1=CC=CC=C1
InChI Identifier
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)
InChI KeyXWLUWCNOOVRFPX-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as diphenylmethanes. Diphenylmethanes are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • Alpha-amino acid or derivatives
  • N-acyl urea
  • Ureide
  • Monoalkyl phosphate
  • Imidazolinone
  • Organic phosphoric acid derivative
  • Phosphoric acid ester
  • Alkyl phosphate
  • 2-imidazoline
  • Isourea
  • Azacycle
  • Carboxylic acid derivative
  • Carboximidamide
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Organooxygen compound
  • Carbonyl group
  • Organic oxide
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Biological location

Process

Naturally occurring process

Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.14 g/LNot Available
LogPNot AvailableNot Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.14 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity87.05 m³·mol⁻¹ChemAxon
Polarizability33.23 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+181.85731661259
DarkChem[M-H]-177.85431661259
DeepCCS[M+H]+168.40330932474
DeepCCS[M-H]-166.04530932474
DeepCCS[M-2H]-199.10930932474
DeepCCS[M+Na]+174.49630932474
AllCCS[M+H]+181.532859911
AllCCS[M+H-H2O]+178.432859911
AllCCS[M+NH4]+184.432859911
AllCCS[M+Na]+185.232859911
AllCCS[M-H]-178.832859911
AllCCS[M+Na-2H]-178.532859911
AllCCS[M+HCOO]-178.232859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
FosphenytoinOP(O)(=O)OCN1C(=O)NC(C1=O)(C1=CC=CC=C1)C1=CC=CC=C14203.1Standard polar33892256
FosphenytoinOP(O)(=O)OCN1C(=O)NC(C1=O)(C1=CC=CC=C1)C1=CC=CC=C12763.6Standard non polar33892256
FosphenytoinOP(O)(=O)OCN1C(=O)NC(C1=O)(C1=CC=CC=C1)C1=CC=CC=C13087.8Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Fosphenytoin,1TMS,isomer #1C[Si](C)(C)OP(=O)(O)OCN1C(=O)NC(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O3127.2Semi standard non polar33892256
Fosphenytoin,1TMS,isomer #1C[Si](C)(C)OP(=O)(O)OCN1C(=O)NC(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O2915.8Standard non polar33892256
Fosphenytoin,1TMS,isomer #1C[Si](C)(C)OP(=O)(O)OCN1C(=O)NC(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O4296.1Standard polar33892256
Fosphenytoin,1TMS,isomer #2C[Si](C)(C)N1C(=O)N(COP(=O)(O)O)C(=O)C1(C1=CC=CC=C1)C1=CC=CC=C12854.8Semi standard non polar33892256
Fosphenytoin,1TMS,isomer #2C[Si](C)(C)N1C(=O)N(COP(=O)(O)O)C(=O)C1(C1=CC=CC=C1)C1=CC=CC=C12870.8Standard non polar33892256
Fosphenytoin,1TMS,isomer #2C[Si](C)(C)N1C(=O)N(COP(=O)(O)O)C(=O)C1(C1=CC=CC=C1)C1=CC=CC=C14455.3Standard polar33892256
Fosphenytoin,2TMS,isomer #1C[Si](C)(C)OP(=O)(OCN1C(=O)NC(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O)O[Si](C)(C)C3107.1Semi standard non polar33892256
Fosphenytoin,2TMS,isomer #1C[Si](C)(C)OP(=O)(OCN1C(=O)NC(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O)O[Si](C)(C)C2979.5Standard non polar33892256
Fosphenytoin,2TMS,isomer #1C[Si](C)(C)OP(=O)(OCN1C(=O)NC(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O)O[Si](C)(C)C3836.6Standard polar33892256
Fosphenytoin,2TMS,isomer #2C[Si](C)(C)OP(=O)(O)OCN1C(=O)N([Si](C)(C)C)C(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O2891.7Semi standard non polar33892256
Fosphenytoin,2TMS,isomer #2C[Si](C)(C)OP(=O)(O)OCN1C(=O)N([Si](C)(C)C)C(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O2872.9Standard non polar33892256
Fosphenytoin,2TMS,isomer #2C[Si](C)(C)OP(=O)(O)OCN1C(=O)N([Si](C)(C)C)C(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O3866.7Standard polar33892256
Fosphenytoin,3TMS,isomer #1C[Si](C)(C)OP(=O)(OCN1C(=O)N([Si](C)(C)C)C(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O)O[Si](C)(C)C2943.0Semi standard non polar33892256
Fosphenytoin,3TMS,isomer #1C[Si](C)(C)OP(=O)(OCN1C(=O)N([Si](C)(C)C)C(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O)O[Si](C)(C)C2931.6Standard non polar33892256
Fosphenytoin,3TMS,isomer #1C[Si](C)(C)OP(=O)(OCN1C(=O)N([Si](C)(C)C)C(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O)O[Si](C)(C)C3469.6Standard polar33892256
Fosphenytoin,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)OP(=O)(O)OCN1C(=O)NC(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O3360.9Semi standard non polar33892256
Fosphenytoin,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)OP(=O)(O)OCN1C(=O)NC(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O3129.5Standard non polar33892256
Fosphenytoin,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)OP(=O)(O)OCN1C(=O)NC(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O4404.6Standard polar33892256
Fosphenytoin,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)N1C(=O)N(COP(=O)(O)O)C(=O)C1(C1=CC=CC=C1)C1=CC=CC=C13163.9Semi standard non polar33892256
Fosphenytoin,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)N1C(=O)N(COP(=O)(O)O)C(=O)C1(C1=CC=CC=C1)C1=CC=CC=C13090.9Standard non polar33892256
Fosphenytoin,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)N1C(=O)N(COP(=O)(O)O)C(=O)C1(C1=CC=CC=C1)C1=CC=CC=C14395.0Standard polar33892256
Fosphenytoin,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)OP(=O)(OCN1C(=O)NC(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O)O[Si](C)(C)C(C)(C)C3536.9Semi standard non polar33892256
Fosphenytoin,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)OP(=O)(OCN1C(=O)NC(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O)O[Si](C)(C)C(C)(C)C3342.6Standard non polar33892256
Fosphenytoin,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)OP(=O)(OCN1C(=O)NC(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O)O[Si](C)(C)C(C)(C)C4070.1Standard polar33892256
Fosphenytoin,2TBDMS,isomer #2CC(C)(C)[Si](C)(C)OP(=O)(O)OCN1C(=O)N([Si](C)(C)C(C)(C)C)C(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O3365.3Semi standard non polar33892256
Fosphenytoin,2TBDMS,isomer #2CC(C)(C)[Si](C)(C)OP(=O)(O)OCN1C(=O)N([Si](C)(C)C(C)(C)C)C(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O3268.9Standard non polar33892256
Fosphenytoin,2TBDMS,isomer #2CC(C)(C)[Si](C)(C)OP(=O)(O)OCN1C(=O)N([Si](C)(C)C(C)(C)C)C(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O3917.3Standard polar33892256
Fosphenytoin,3TBDMS,isomer #1CC(C)(C)[Si](C)(C)OP(=O)(OCN1C(=O)N([Si](C)(C)C(C)(C)C)C(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O)O[Si](C)(C)C(C)(C)C3514.4Semi standard non polar33892256
Fosphenytoin,3TBDMS,isomer #1CC(C)(C)[Si](C)(C)OP(=O)(OCN1C(=O)N([Si](C)(C)C(C)(C)C)C(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O)O[Si](C)(C)C(C)(C)C3480.2Standard non polar33892256
Fosphenytoin,3TBDMS,isomer #1CC(C)(C)[Si](C)(C)OP(=O)(OCN1C(=O)N([Si](C)(C)C(C)(C)C)C(C2=CC=CC=C2)(C2=CC=CC=C2)C1=O)O[Si](C)(C)C(C)(C)C3653.0Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Fosphenytoin GC-MS (Non-derivatized) - 70eV, Positivesplash10-00ls-4941000000-7f020f5c4237af5bfb3c2017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Fosphenytoin GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Fosphenytoin 10V, Positive-QTOFsplash10-03di-0019000000-801dc353a42886feac152016-06-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Fosphenytoin 20V, Positive-QTOFsplash10-03dj-1019000000-954988a4832c09ddde712016-06-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Fosphenytoin 40V, Positive-QTOFsplash10-0uy0-5931000000-a2e668ce8b6003249e522016-06-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Fosphenytoin 10V, Negative-QTOFsplash10-03di-2009000000-f100b603f8bec4297f642016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Fosphenytoin 20V, Negative-QTOFsplash10-004i-9100000000-974b8eaa512f665645c72016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Fosphenytoin 40V, Negative-QTOFsplash10-002f-9000000000-edcf929c72670ddaeafe2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Fosphenytoin 10V, Positive-QTOFsplash10-03di-0029000000-80555bf6b08b1edde5ba2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Fosphenytoin 20V, Positive-QTOFsplash10-014i-0191000000-7ba4d52b46cd243852002021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Fosphenytoin 40V, Positive-QTOFsplash10-0159-0920000000-be8b0958365f6e0346ab2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Fosphenytoin 10V, Negative-QTOFsplash10-03di-0009000000-cc4d0db2ee88412c5f882021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Fosphenytoin 20V, Negative-QTOFsplash10-0udi-0944000000-f5c9d9bf3cb087cf76852021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Fosphenytoin 40V, Negative-QTOFsplash10-00p0-5930000000-1c6b6a79ed38b9c1414a2021-10-11Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01320 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01320 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01320
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID50839
KEGG Compound IDC07840
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkFosphenytoin
METLIN IDNot Available
PubChem Compound56339
PDB IDNot Available
ChEBI ID775287
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Browne TR, Kugler AR, Eldon MA: Pharmacology and pharmacokinetics of fosphenytoin. Neurology. 1996 Jun;46(6 Suppl 1):S3-7. [PubMed:8649612 ]
  2. Johnson J, Wrenn K: Inappropriate fosphenytoin use in the ED. Am J Emerg Med. 2001 Jul;19(4):293-4. [PubMed:11447516 ]
  3. Applebaum J, Levine J, Belmaker RH: Intravenous fosphenytoin in acute mania. J Clin Psychiatry. 2003 Apr;64(4):408-9. [PubMed:12716241 ]
  4. McCleane GJ: Intravenous infusion of fosphenytoin produces prolonged pain relief: a case report. J Pain. 2002 Apr;3(2):156-8. [PubMed:14622802 ]
  5. Luszczki JJ: Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions. Pharmacol Rep. 2009 Mar-Apr;61(2):197-216. [PubMed:19443931 ]

Enzymes

General function:
Involved in monooxygenase 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 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. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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. [PubMed:18473749 ]
General function:
Involved in monooxygenase 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 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.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
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. [PubMed:19202563 ]
  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. Goldstein JA: Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Br J Clin Pharmacol. 2001 Oct;52(4):349-55. [PubMed:11678778 ]
  4. Klotz U: The role of pharmacogenetics in the metabolism of antiepileptic drugs: pharmacokinetic and therapeutic implications. Clin Pharmacokinet. 2007;46(4):271-9. [PubMed:17375979 ]
General function:
Involved in monooxygenase 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 imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular weight:
55944.565
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. [PubMed:18367977 ]
  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. [PubMed:19617466 ]
  3. Klotz U: The role of pharmacogenetics in the metabolism of antiepileptic drugs: pharmacokinetic and therapeutic implications. Clin Pharmacokinet. 2007;46(4):271-9. [PubMed:17375979 ]
General function:
Involved in monooxygenase 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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular weight:
56277.81
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. [PubMed:15123723 ]
  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. [PubMed:14977870 ]
General function:
Involved in monooxygenase 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 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).
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular weight:
55824.275
References
  1. 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. [PubMed:12920163 ]
General function:
Involved in ion channel activity
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 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
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular weight:
226937.5
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. [PubMed:15001403 ]
  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. [PubMed:20298965 ]
  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. [PubMed:15066664 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]