Details
Stereochemistry | ACHIRAL |
Molecular Formula | C16H15N2O6P |
Molecular Weight | 362.2739 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OP(O)(=O)OCN1C(=O)NC(C1=O)(C2=CC=CC=C2)C3=CC=CC=C3
InChI
InChIKey=XWLUWCNOOVRFPX-UHFFFAOYSA-N
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)
Molecular Formula | C16H15N2O6P |
Molecular Weight | 362.2739 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/8981053Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020450s020lbl.pdf
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8981053
Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020450s020lbl.pdf
Phenytoin is an anti-epileptic drug. Phenytoin has been used with much clinical success against all types of epileptiform seizures, except petit mal epilepsy. Phenytoin is a available for oral administration (tablets, capsules, suspension). CEREBYX® (fosphenytoin sodium injection) is a prodrug intended for parenteral administration; its active metabolite is phenytoin. CEREBYX should be used only when oral phenytoin administration is not possible. Although several potential targets for phenytoin action have been identified within the CNS (Na-K-ATPase, the GABAA receptor complex, ionotropic glutamate receptors, calcium channels and sigma binding sites) to date, though, the best evidence hinges on the inhibition of voltage-sensitive Na+ channels in the plasma membrane of neurons undergoing seizure activity.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4187 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8981053 |
10.4 µM [EC50] | ||
Target ID: CHEMBL5163 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8981053 |
52.5 µM [EC50] | ||
Target ID: CHEMBL5202 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8981053 |
20.0 µM [EC50] | ||
Target ID: CHEMBL1845 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8981053 |
19.9 µM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | DILANTIN-125 Approved UseDilantin (phenytoin) is indicated for the control of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures Launch Date1953 |
|||
Primary | CEREBYX Approved UseCEREBYX is indicated for the control of generalized tonic-clonic status epilepticus and prevention and treatment of seizures occurring during neurosurgery. CEREBYX can also be substituted, short-term, for oral phenytoin. CEREBYX should be used only when oral phenytoin administration is not possible. CEREBYX must not be given orally. Launch Date1996 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.176 μg/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
PHENYTOIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
32.172 μg × h/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
PHENYTOIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
15.49 h |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
PHENYTOIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
600 mg single, oral Highest studied dose Dose: 600 mg Route: oral Route: single Dose: 600 mg Sources: |
unhealthy, 31 years n = 15 Health Status: unhealthy Condition: epilepsy Age Group: 31 years Sex: M+F Population Size: 15 Sources: |
|
20 g single, oral Overdose Dose: 20 g Route: oral Route: single Dose: 20 g Co-administed with:: glibenclamide(500 mg) Sources: |
unhealthy, 41 years n = 1 Health Status: unhealthy Age Group: 41 years Sex: F Population Size: 1 Sources: |
Other AEs: Sinus bradycardia, Hypotension... Other AEs: Sinus bradycardia (1 patient) Sources: Hypotension (severe, 1 patient) |
5 g single, oral Overdose |
unhealthy, 49 years n = 1 Health Status: unhealthy Age Group: 49 years Sex: M Population Size: 1 Sources: |
Other AEs: Acute respiratory failure... |
60 mg/kg multiple, intravenous (total) Overdose Dose: 60 mg/kg Route: intravenous Route: multiple Dose: 60 mg/kg Sources: |
unhealthy, 7 years n = 1 Health Status: unhealthy Age Group: 7 years Sex: M Population Size: 1 Sources: |
Other AEs: Encephalopathy... |
2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Nystagmus, Ataxia... Other AEs: Nystagmus (grade 5) Sources: Ataxia (grade 5) Dysarthria (grade 5) Tremor (grade 5) Hyperreflexia (grade 5) Lethargy (grade 5) Slurred speech (grade 5) Blurred vision (grade 5) Nausea (grade 5) Vomiting (grade 5) |
10 mg/kg single, intramuscular (starting) Dose: 10 mg/kg Route: intramuscular Route: single Dose: 10 mg/kg Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Hypotension, Cardiac arrhythmias... Other AEs: Hypotension (severe) Sources: Cardiac arrhythmias |
10 mg/kg single, intravenous (starting) Dose: 10 mg/kg Route: intravenous Route: single Dose: 10 mg/kg Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Hypotension, Cardiac arrhythmias... Other AEs: Hypotension (severe) Sources: Cardiac arrhythmias |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Sinus bradycardia | 1 patient | 20 g single, oral Overdose Dose: 20 g Route: oral Route: single Dose: 20 g Co-administed with:: glibenclamide(500 mg) Sources: |
unhealthy, 41 years n = 1 Health Status: unhealthy Age Group: 41 years Sex: F Population Size: 1 Sources: |
Hypotension | severe, 1 patient | 20 g single, oral Overdose Dose: 20 g Route: oral Route: single Dose: 20 g Co-administed with:: glibenclamide(500 mg) Sources: |
unhealthy, 41 years n = 1 Health Status: unhealthy Age Group: 41 years Sex: F Population Size: 1 Sources: |
Acute respiratory failure | 1 patient | 5 g single, oral Overdose |
unhealthy, 49 years n = 1 Health Status: unhealthy Age Group: 49 years Sex: M Population Size: 1 Sources: |
Encephalopathy | 1 patient | 60 mg/kg multiple, intravenous (total) Overdose Dose: 60 mg/kg Route: intravenous Route: multiple Dose: 60 mg/kg Sources: |
unhealthy, 7 years n = 1 Health Status: unhealthy Age Group: 7 years Sex: M Population Size: 1 Sources: |
Ataxia | grade 5 | 2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Blurred vision | grade 5 | 2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Dysarthria | grade 5 | 2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Hyperreflexia | grade 5 | 2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Lethargy | grade 5 | 2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Nausea | grade 5 | 2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Nystagmus | grade 5 | 2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Slurred speech | grade 5 | 2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Tremor | grade 5 | 2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Vomiting | grade 5 | 2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Cardiac arrhythmias | 10 mg/kg single, intramuscular (starting) Dose: 10 mg/kg Route: intramuscular Route: single Dose: 10 mg/kg Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
|
Hypotension | severe | 10 mg/kg single, intramuscular (starting) Dose: 10 mg/kg Route: intramuscular Route: single Dose: 10 mg/kg Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Cardiac arrhythmias | 10 mg/kg single, intravenous (starting) Dose: 10 mg/kg Route: intravenous Route: single Dose: 10 mg/kg Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
|
Hypotension | severe | 10 mg/kg single, intravenous (starting) Dose: 10 mg/kg Route: intravenous Route: single Dose: 10 mg/kg Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/15961125/ Page: 6.0 |
weak | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/15933229/ Page: 7.0 |
yes [IC50 145 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/15933229/ Page: 7.0 |
yes [IC50 280 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/15933229/ Page: 7.0 |
yes [IC50 607 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/9606477 |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/9332469/ |
yes | likely (co-administration study) Comment: See https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page=10 Sources: https://pubmed.ncbi.nlm.nih.gov/9332469/ |
||
Sources: https://pubmed.ncbi.nlm.nih.gov/15247556/ |
yes | likely (co-administration study) Comment: See https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page=10 Sources: https://pubmed.ncbi.nlm.nih.gov/15247556/ |
||
Sources: https://pubmed.ncbi.nlm.nih.gov/26721703/ Page: 46.0 |
yes | likely (co-administration study) Comment: See https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page=11 Sources: https://pubmed.ncbi.nlm.nih.gov/26721703/ Page: 46.0 |
||
Sources: https://pubmed.ncbi.nlm.nih.gov/15247556/ |
yes | likely (co-administration study) Comment: See https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page=9 Sources: https://pubmed.ncbi.nlm.nih.gov/15247556/ |
||
Sources: https://pubmed.ncbi.nlm.nih.gov/9606477 |
yes | likely (co-administration study) Comment: See https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page=11 Sources: https://pubmed.ncbi.nlm.nih.gov/9606477 |
||
yes | yes (co-administration study) Comment: mean AUC(0-24) of losartan was insignificantly increased by 17% when losartan was coadministered with phenytoin. See more on https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page=9 Sources: https://pubmed.ncbi.nlm.nih.gov/12235444/ |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/15961125/ Page: 6.0 |
no | |||
Page: 8.0 |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/8819299/ Page: 7.0 |
yes | |||
yes | likely (co-administration study) Comment: See https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page=9 Sources: https://pubmed.ncbi.nlm.nih.gov/11038165/ |
|||
yes | yes (co-administration study) Comment: Coadministration of losartan had no effect on the pharmacokinetics of phenytoin. See more on https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page8 Page: 8.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Harmful effect of megadoses of vitamins: electroencephalogram abnormalities and seizures induced by intravenous folate in drug-treated epileptics. | 1975 Jan |
|
The influence of aldosterone and anticonvulsant drugs on electroencephalographic and clinical disturbances induced by the spirolactone derivative, potassium canrenoate. | 1975 Jan |
|
[Atrioventricular junctional arrhythmia due to oral phenytoin intoxication]. | 1999 Mar 15 |
|
Acute fulminant hepatic failure in a woman treated with phenytoin and trimethoprim-sulfamethoxazole. | 2000 Dec |
|
Phenytoin, midazolam, and naloxone protect against fentanyl-induced brain damage in rats. | 2000 Dec |
|
Images in clinical medicine. Gingival hyperplasia induced by phenytoin. | 2000 Feb 3 |
|
An embryoprotective role for glucose-6-phosphate dehydrogenase in developmental oxidative stress and chemical teratogenesis. | 2000 Jan |
|
Phenytoin poisoning after using Chinese proprietary medicines. | 2000 Jul |
|
Cerebral edema with herniation during acetaminophen-induced fulminant hepatic failure. | 2000 Jul |
|
Refractory idiopathic absence status epilepticus: A probable paradoxical effect of phenytoin and carbamazepine. | 2000 Jul |
|
Phenytoin and cyclosporin A suppress the expression of MMP-1, TIMP-1, and cathepsin L, but not cathepsin B in cultured gingival fibroblasts. | 2000 Jun |
|
Incidence of intravenous site reactions in neurotrauma patients receiving valproate or phenytoin. | 2000 Jun |
|
Catalytic activity of three variants (Ile, Leu, and Thr) at amino acid residue 359 in human CYP2C9 gene and simultaneous detection using single-strand conformation polymorphism analysis. | 2000 Jun |
|
Seizure-inducing paradoxical reaction to antiepileptic drugs. | 2000 Jun |
|
Purple glove syndrome caused by oral administration of phenytoin. | 2000 Nov |
|
Effects of combined administration of zonisamide and valproic acid or phenytoin to nitric oxide production, monoamines and zonisamide concentrations in the brain of seizure-susceptible EL mice. | 2000 Sep 15 |
|
Drugs for discoid lupus erythematosus. | 2001 |
|
II. An altered proliferation response due to the anticonvulsant phenytoin (PHT) in epileptic patients. | 2001 |
|
I. The modulatory effect in genotoxic responses due to age and duration of PHT-therapy in epileptic patients. | 2001 |
|
Evaluation of the neuroprotective effects of sodium channel blockers after spinal cord injury: improved behavioral and neuroanatomical recovery with riluzole. | 2001 Apr |
|
Performance characteristics of four free phenytoin immunoassays. | 2001 Apr |
|
Rocuronium-induced neuromuscular blockade is affected by chronic phenytoin therapy. | 2001 Apr |
|
Stereoselective determination of p-hydroxyphenyl-phenylhydantoin enantiomers in rat liver microsomal incubates by reversed-phase high-performance liquid chromatography using beta-cyclodextrin as chiral mobile phase additives. | 2001 Apr |
|
Decreases in phenytoin hydroxylation activities catalyzed by liver microsomal cytochrome P450 enzymes in phenytoin-treated rats. | 2001 Apr |
|
Inhibition of phenytoin hydroxylation in human liver microsomes by several selective serotonin re-uptake inhibitors. | 2001 Apr |
|
The teratogenicity of anticonvulsant drugs. | 2001 Apr 12 |
|
Nitroso-urea-cisplatin-based chemotherapy associated with valproate: increase of haematologic toxicity. | 2001 Feb |
|
Determination of the antiepileptics vigabatrin and gabapentin in dosage forms and biological fluids using Hantzsch reaction. | 2001 Feb |
|
Refractory idiopathic status epilepticus. | 2001 Feb |
|
Cardiac arrest after fast intravenous infusion of phenytoin mistaken for fosphenytoin. | 2001 Feb |
|
Antiepileptic drug withdrawal in patients with temporal lobe epilepsy undergoing presurgical video-EEG monitoring. | 2001 Feb |
|
Fosphenytoin: pharmacokinetics and tolerance of intramuscular loading doses. | 2001 Feb |
|
Glutamate receptor antagonists differentially affect the protective activity of conventional antiepileptics against amygdala-kindled seizures in rats. | 2001 Feb |
|
Phenytoin intoxication induced by fluvoxamine. | 2001 Feb |
|
[Maintenance dose requirement for phenytoin is lowered in genetically impaired drug metabolism independent of concommitant use of other antiepileptics]. | 2001 Feb 17 |
|
[Febrile convulsions, Treatment and prognosis]. | 2001 Feb 19 |
|
Interferon-alpha2a and 13-cis-retinoic acid with radiation treatment for high-grade glioma. | 2001 Jan |
|
Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors. | 2001 Jan |
|
Electrophysiological and pharmacological properties of the human brain type IIA Na+ channel expressed in a stable mammalian cell line. | 2001 Jan |
|
Effects of antiepileptic drugs on rat platelet aggregation: ex vivo and in vitro study. | 2001 Jan |
|
Effects of phenytoin on glutathione status and oxidative stress biomarker gene mRNA levels in cultured precision human liver slices. | 2001 Jan |
|
Successful treatment of antiepileptic drug hypersensitivity syndrome with intravenous immune globulin. | 2001 Jan |
|
[Lamotrigine in refractory partial and general epilepsies]. | 2001 Jan 1-15 |
|
N6-cyclohexyladenosine and 3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid enhance the effect of antiepileptic drugs against induced seizures in mice. | 2001 Jan-Apr |
|
Volume-selective proton MR spectroscopy for in-vitro quantification of anticonvulsants. | 2001 Mar |
|
Fosphenytoin in infants of extremely low birth weight. | 2001 Mar |
|
Influence of retigabine on the anticonvulsant activity of some antiepileptic drugs against audiogenic seizures in DBA/2 mice. | 2001 Mar |
|
Phenytoin-induced cleft palate: evidence for embryonic cardiac bradyarrhythmia due to inhibition of delayed rectifier K+ channels resulting in hypoxia-reoxygenation damage. | 2001 Mar |
|
Interaction of plasma proteins with cytochromes P450 mediated metabolic reactions: inhibition by human serum albumin and alpha-globulins of the debrisoquine 4-hydroxylation (CYP2D) in liver microsomes of human, hamster and rat. | 2001 Mar 8 |
|
Efficacy of levetiracetam versus fosphenytoin for the recurrence of seizures after status epilepticus. | 2017 Jun |
Sample Use Guides
Dilantin-125® (Phenytoin Oral Suspension, USP), each 5 ml of suspension contains 125 mg of phenytoin: Patients who have received no previous treatment may be started on one teaspoonful (5 mL) of Dilantin-125 Suspension three times daily, and the dose is then adjusted to suit individual requirements. An increase to five teaspoonfuls daily may be made, if necessary.
CEREBYX® (fosphenytoin sodium injection) is a prodrug intended for parenteral administration; its active metabolite is phenytoin. 1.5 mg of fosphenytoin sodium is equivalent to
1 mg phenytoin sodium, and is referred to as 1 mg phenytoin sodium equivalents (PE). CEREBYX should be used only when oral phenytoin administration is not possible.
Dosage (Status Epilepticus): The loading dose of CEREBYX is 15 to 20 mg PE/kg administered at 100 to 150 mg PE/min.
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27522920
Exposure of human adult keratinocytes (HaCaT cells) for 48 h to alkyd nanoemulsions producing phenytoin concentrations of 3.125-200 μg/mL resulted in relative cell viability readings using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide of 100% confirming nontoxicity and suggesting cell proliferation activity.
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:46:31 GMT 2023
by
admin
on
Fri Dec 15 15:46:31 GMT 2023
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Record UNII |
B4SF212641
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000008486
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WHO-ATC |
N03AB05
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WHO-VATC |
QN03AB05
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NCI_THESAURUS |
C264
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LIVERTOX |
NBK547879
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NDF-RT |
N0000175753
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FDA ORPHAN DRUG |
55790
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DTXSID9044299
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C65766
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FOSPHENYTOIN
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SUB07804MIG
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7523
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B4SF212641
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100000080442
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Fosphenytoin
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7190
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56339
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CHEMBL1201336
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DB01320
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C043114
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72236
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6484
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1247
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93390-81-9
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m5555
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PRIMARY | Merck Index |
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SALT/SOLVATE -> PARENT |
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METABOLIC ENZYME -> INDUCER | |||
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SALT/SOLVATE -> PARENT |
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BINDING
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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