Identification

Name
Fosphenytoin
Accession Number
DB01320
Type
Small Molecule
Groups
Approved, Investigational
Description

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.

Structure
Thumb
Synonyms
  • (3-Phosphoryloxymethyl)phenytoin
  • Fosfenitoina
  • Fosphenytoin
  • Fosphenytoine
  • Fosphenytoinum
Product Ingredients
IngredientUNIICASInChI Key
Fosphenytoin sodium7VLR55452Z92134-98-0GQPXYJNXTAFDLT-UHFFFAOYSA-L
Active Moieties
NameKindUNIICASInChI Key
Phenytoinprodrug6158TKW0C557-41-0CXOFVDLJLONNDW-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CerebyxInjection, solution50 mg/1mLIntramuscular; IntravenousPfizer Laboratories Div Pfizer Inc2013-10-28Not applicableUs
CerebyxLiquid75 mgIntramuscular; IntravenousErfa Canada 2012 Inc2000-03-01Not applicableCanada
CerebyxInjection, solution50 mg/1mLIntramuscular; IntravenousPfizer Laboratories Div Pfizer Inc2013-10-28Not applicableUs
CerebyxInjection, solution50 mg/1mLIntramuscular; IntravenousParke Davis Div Of Pfizer Inc1996-08-052010-01-01Us
CerebyxInjection, solution50 mg/1mLIntramuscular; IntravenousPfizer Laboratories Div Pfizer Inc2013-10-28Not applicableUs
CerebyxInjection, solution50 mg/1mLIntramuscular; IntravenousParke Davis Div Of Pfizer Inc1996-08-052010-01-01Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FosphenytoinInjection, solution50 mg/1mLIntramuscular; IntravenousFresenius Kabi2009-12-14Not applicableUs
Fosphenytoin SodiumInjection, solution50 mg/1mLIntramuscular; IntravenousHikma Farmaceutica2009-12-022009-12-02Us
Fosphenytoin SodiumInjection50 mg/1mLIntramuscular; IntravenousWockhardt2007-08-06Not applicableUs
Fosphenytoin SodiumInjection, solution50 mg/1mLIntramuscular; IntravenousSun Pharma Global FZE2009-08-142017-01-23Us
Fosphenytoin SodiumInjection, solution75 mg/1mLIntramuscular; IntravenousBaxter Laboratories2007-08-062009-06-28Us
Fosphenytoin SodiumInjection50 mg/1mLIntramuscular; IntravenousAmneal Biosciences2016-07-25Not applicableUs
Fosphenytoin SodiumInjection50 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2007-09-142011-08-31Us
Fosphenytoin SodiumInjection50 mg/1mLIntramuscular; IntravenousApotex Corporation2007-08-062010-10-14Us
Fosphenytoin SodiumInjection50 mg/1mLIntramuscular; IntravenousAmneal Pharmaceuticals of New York Llc2013-05-17Not applicableUs
Fosphenytoin SodiumInjection, solution50 mg/1mLIntramuscular; IntravenousGenera Medix Inc.2007-08-062010-12-29Us
International/Other Brands
Cerebyx / Prodilantin
Categories
UNII
B4SF212641
CAS number
93390-81-9
Weight
Average: 362.2739
Monoisotopic: 362.066772734
Chemical Formula
C16H15N2O6P
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

Pharmacology

Indication

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.

Associated Conditions
Pharmacodynamics

Fosphenytoin is a water-soluble phenytoin prodrug used only in hospitals for the treatment of epileptic seizures. Following parenteral administration of fosphenytoin, fosphenytoin is converted to the anticonvulsant phenytoin by endogenous phosphatases. For every mmol of fosphenytoin administered, one mmol of phenytoin is produced. The pharmacological and toxicological effects of fosphenytoin include those of phenytoin.

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
Human
Absorption

Fosphenytoin is completely bioavailable following lM administration.

Volume of distribution
  • 4.3 to 10.8 L
Protein binding

Extensively bound (95% to 99%) to human plasma proteins, primarily albumin.

Metabolism

Hepatic.

Route of elimination

Phenytoin derived from administration of Cerebyx is extensively metabolized in the liver and excreted in urine primarily as 5-(p-hydroxyphenyl)-5-phenylhydantoin and its glucuronide; little unchanged phenytoin (1%–5% of the Cerebyx dose) is recovered in urine.

Half life

Fosphenytoin has a half-life of approximately 15 minutes.

Clearance
Not Available
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.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Fosphenytoin (Antiarrhythmic) Metabolism PathwayDrug metabolism
Fosphenytoin (Antiarrhythmic) Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
16-BromoepiandrosteroneThe serum concentration of 16-Bromoepiandrosterone can be decreased when it is combined with Fosphenytoin.
19-norandrostenedioneThe serum concentration of 19-norandrostenedione can be decreased when it is combined with Fosphenytoin.
2-mercaptobenzothiazoleThe serum concentration of 2-mercaptobenzothiazole can be decreased when it is combined with Fosphenytoin.
5-androstenedioneThe serum concentration of 5-androstenedione can be decreased when it is combined with Fosphenytoin.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Fosphenytoin is combined with 7-Nitroindazole.
AbemaciclibThe serum concentration of Abemaciclib can be decreased when it is combined with Fosphenytoin.
AbirateroneThe serum concentration of Abiraterone can be decreased when it is combined with Fosphenytoin.
AceclofenacThe metabolism of Aceclofenac can be increased when combined with Fosphenytoin.
AcenocoumarolFosphenytoin may increase the anticoagulant activities of Acenocoumarol.
AcepromazineThe risk or severity of adverse effects can be increased when Fosphenytoin is combined with Acepromazine.
Food Interactions
  • Avoid alcohol.
  • Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication.
  • Take with food.

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. [PubMed:11447516]
  2. Applebaum J, Levine J, Belmaker RH: Intravenous fosphenytoin in acute mania. J Clin Psychiatry. 2003 Apr;64(4):408-9. [PubMed:12716241]
  3. McCleane GJ: Intravenous infusion of fosphenytoin produces prolonged pain relief: a case report. J Pain. 2002 Apr;3(2):156-8. [PubMed:14622802]
  4. Browne TR, Kugler AR, Eldon MA: Pharmacology and pharmacokinetics of fosphenytoin. Neurology. 1996 Jun;46(6 Suppl 1):S3-7. [PubMed:8649612]
  5. Luszczki JJ: Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions. Pharmacol Rep. 2009 Mar-Apr;61(2):197-216. [PubMed:19443931]
External Links
Human Metabolome Database
HMDB0015417
KEGG Compound
C07840
PubChem Compound
56339
PubChem Substance
46505168
ChemSpider
50839
ChEBI
5165
ChEMBL
CHEMBL1201336
Therapeutic Targets Database
DAP000520
PharmGKB
PA164746820
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Fosphenytoin
ATC Codes
N03AB05 — Fosphenytoin
AHFS Codes
  • 28:12.12 — Hydantoins
FDA label
Download (820 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentNonconvulsive Seizures1
3CompletedTreatmentEpilepsies1
3RecruitingTreatmentBenzodiazepine Refractory Status Epilepticus1
3RecruitingTreatmentEpilepsies / Refractory seizure disorders1
4CompletedTreatmentGrand mal Generalized tonic-clonic seizure1
Not AvailableRecruitingNot AvailableAcute Bacterial Exacerbation of Chronic Bronchitis (ABECB) / Acute Bacterial Sinusitis (ABS) / Acute Decompensated Heart Failure (ADHF) / Acute Pyelonephritis / Adenovirus / Adjunct to general anesthesia therapy / Adrenal Insufficiency / Airway Swelling / Anaesthesia therapy / Anxiolysis / Arterial Hypotension / Autism, Early Infantile / Autistic Disorder / Bartonellosis / Benzodiazepine Withdrawal / Benzodiazepines / Bipolar Disorder (BD) / Bloodstream Infections / Bone and Joint Infections / Brain Swelling / Bronchospasm / Brucellosis / Cardiac Arrest / Central Nervous System Infections / Cholera / Chronic Bacterial Prostatitis / Community Acquired Pneumonia (CAP) / Complicated Urinary Tract Infections / Convulsions / Cyanide Poisoning / Cytomegalovirus Retinitis / Drug hypersensitivity reaction / Early-onset Schizophrenia Spectrum Disorders / Edema / Epilepsies / Feeling Anxious / Flu caused by Influenza / Gastroparesis / Gynaecological infection / Headaches / Herpes Simplex Virus / High Blood Pressure (Hypertension) / High Cholesterol / Hospital-acquired bacterial pneumonia / Hyperlipidemias / Infantile Hemangiomas / Infection NOS / Inflammatory Conditions / Inflammatory Reaction / Influenza Treatment or Prophylaxis / Inhalational Anthrax (Post-Exposure) / Intra-Abdominal Infections / Life-threatening Fungal Infections / Lower Respiratory Tract Infection (LRTI) / Meningitis, Bacterial / Migraines / Muscle Spasms / Nausea / Opioid Addiction / Pain / Plague / Pneumonia / Prophylaxis / Psittacosis / Q Fever / Reflux / Relapsing Fever / Rocky Mountain Spotted Fever / Schizophrenic Disorders / Sedation therapy / Seizures / Sepsis / Skeletal Muscle Spasms / Skin and Subcutaneous Tissue Bacterial Infections / Skin Structures and Soft Tissue Infections / Stable Angina (SA) / Thromboprophylaxis / Thrombosis / Trachoma / Treatment-resistant Schizophrenia / Tularemia / Typhus Fever / Uncomplicated Skin and Skin Structure Infections / Uncomplicated Urinary Tract Infections / Urinary Tract Infections (UTIs) / Vomiting / Withdrawal1
Not AvailableTerminatedPreventionTraumatic Brain Injury (TBI)1
Not AvailableTerminatedTreatmentSubarachnoid Hemorrhage1

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
LiquidIntramuscular; Intravenous75 mg
InjectionIntramuscular; Intravenous50 mg/1mL
InjectionIntravenous50 mg/1mL
Injection, solutionIntramuscular; Intravascular50 mg/1mL
Injection, solutionIntramuscular; Intravenous50 mg/1mL
Injection, 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
Not Available

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-MSNot Available
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

Taxonomy

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
Diphenylmethane / Alpha-amino acid or derivatives / N-acyl urea / Ureide / Monoalkyl phosphate / Imidazolinone / Organic phosphoric acid derivative / Phosphoric acid ester / Alkyl phosphate / 2-imidazoline
show 16 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazolidine-2,4-dione (CHEBI:5165)

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. 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]

Enzymes

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
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. [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]
  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. [PubMed:12920163]
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. 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]
  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. [PubMed:16873909]
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. 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]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. 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]
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. 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]
Kind
Protein
Organism
Human
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. [PubMed:21358975]
  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. [PubMed:29849211]
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]

Carriers

Kind
Protein
Organism
Human
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. [PubMed:8577822]

Drug created on June 30, 2007 11:18 / Updated on September 25, 2018 17:45