Tìm theo
Fosphenytoin
Các tên gọi khác (6 ) :
  • (3-Phosphoryloxymethyl)phenytoin
  • Cerebyx
  • Fosfenitoina
  • Fosphenytoin
  • Fosphenytoine
  • Fosphenytoinum
Thuốc chống co giật, chống động kinh
Thuốc Gốc
Small Molecule
CAS: 93390-81-9
ĐG : Akorn Inc. , http://www.akorn.com
CTHH: C16H15N2O6P
PTK: 362.2739
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.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C16H15N2O6P
Phân tử khối
362.2739
Monoisotopic mass
362.066772734
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)
InChI Key
InChIKey=XWLUWCNOOVRFPX-UHFFFAOYSA-N
IUPAC Name
[(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)methoxy]phosphonic acid
Traditional IUPAC Name
(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)methoxyphosphonic acid
SMILES
OP(O)(=O)OCN1C(=O)NC(C1=O)(C1=CC=CC=C1)C1=CC=CC=C1
Độ hòa tan
1.45e-01 g/l
logP
1.67
logS
-3.4
pKa (strongest acidic)
1.46
pKa (Strongest Basic)
-9.7
PSA
116.17 Å2
Refractivity
87.05 m3·mol-1
Polarizability
33.23 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
5
H Bond Donor Count
3
Physiological Charge
-2
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : 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.
Cơ Chế Tác Dụng : 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. 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.
Dược Động Học :
▧ 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.
Độc Tính : 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.
Chỉ Định : 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.
Tương Tác Thuốc :
  • Acenocoumarol Increased hydantoin levels and risk of bleeding
  • Alprazolam Fosphenytoin may increase the metabolism of alprazolam via CYP3A4.
  • Aminophylline Decreased effect of both products
  • Amiodarone Amiodarone may increase the effect of fosphenytoin.
  • Anisindione Increased hydantoin levels and risk of bleeding
  • Aprepitant The CYP3A4 inducer, fosphenytoin, may decrease the effect of aprepitant.
  • Atracurium Phenytoin decreases the effect of muscle relaxant
  • Betamethasone The enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, betamethasone.
  • Bleomycin The antineoplasic agent decreases the effect of hydantoin
  • Boceprevir Strong CYP3A4 inducers will decrease levels of boceprevir. Concomitant therapy is contraindicated.
  • Capecitabine Capecitabine increases the effect of hydantoin
  • Carboplatin The antineoplasic agent decreases the effect of hydantoin
  • Carmustine The antineoplasic agent decreases the effect of hydantoin
  • Chloramphenicol Increases phenytoin, modifies chloramphenicol
  • Chlordiazepoxide Fosphenytoin may increase the metabolism of chlordiazepoxide via CYP3A4.
  • Chlorotrianisene The enzyme inducer, fosphenytoin, decreases the effect of the hormone agent, chlorotrianisene.
  • Chlorphenamine The antihistamine increases the effect of hydantoin
  • Cimetidine Cimetidine may increase the serum concentration of fosphenytoin by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of fosphenytoin if cimetidine is initiated, discontinued or dose changed.
  • Cisplatin The antineoplasic agent decreases the effect of hydantoin
  • Clarithromycin Clarithromycin may increase the therapeutic and adverse effects of fosphenytoin.
  • Clomifene The enzyme inducer, fosphenytoin, decreases the effect of the hormone agent, clomifene.
  • Clorazepate Fosphenytoin may increase the metabolism of clorazepate via CYP3A4.
  • Clozapine Hydantoin decreases the effect of clozapine
  • Conjugated Estrogens The enzyme inducer, fosphenytoin, decreases the effect of the hormone agent, conjugated estrogens.
  • Cortisone acetate The enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, cortisone acetate.
  • Cyclosporine The hydantoin decreases the effect of cyclosporine
  • Delavirdine The anticonvulsant, fosphenytoin, decreases the effect of delavirdine.
  • Dexamethasone The enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, dexamethasone.
  • Diazepam Fosphenytoin may increase the metabolism of diazepam via CYP3A4.
  • Diazoxide Diazoxide decreases the hydantoin effect
  • Dicoumarol Increased hydantoin levels and risk of bleeding
  • Diethylstilbestrol The enzyme inducer, fosphenytoin, may decrease the therapeutic effect of diethylstilbestrol.
  • Disopyramide The hydantoin decreases the effect of disopyramide
  • Disulfiram Disulfiram may increase the effect of fosphenytoin.
  • Dopamine Risk of severe hypotension
  • Doxacurium chloride Phenytoin decreases the effect of muscle relaxant
  • Doxycycline The anticonvulsant, fosphenytoin, decreases the effect of doxycycline.
  • Dyphylline Decreased effect of both products
  • Estradiol The enzyme inducer, fosphenytoin, decreases the effect of the hormone agent, estradiol.
  • Estradiol valerate/Dienogest Affects CYP3A4 metabolism, decreases or effects levels of Estradiol valerate/Dienogest.
  • Estriol The enzyme inducer, fosphenytoin, decreases the effect of the hormone agent, estriol.
  • Estrone The enzyme inducer, fosphenytoin, decreases the effect of the hormone agent, estrone.
  • Estropipate The enzyme inducer, fosphenytoin, decreases the effect of the hormone agent, estropipate.
  • Ethinyl Estradiol This product may cause a slight decrease of contraceptive effect
  • Etravirine Etravirine, when administered concomitantly with fosphenytoin, may experience a decrease in serum concentration. It is recommended to avoid this combination.
  • Felbamate Increased phenytoin levels and decreased felbamate levels
  • Felodipine The hydantoin decreases the effect of felodipine
  • Fluconazole Fluconazole may increase the effect of hydantoin.
  • Fludrocortisone The enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, fludrocortisone.
  • Fluorouracil Fluorouracil increases the effect of hydantoin
  • Fluoxetine Fluoxetine increases the effect of phenytoin
  • Flurazepam Fosphenytoin may increase the metabolism of flurazepam via CYP3A4.
  • Fluvoxamine Fluvoxamine may increase the therapeutic and adverse effects of fosphenytoin.
  • Folic Acid Folic acid decreases the levels of hydantoin
  • Furosemide The hydantoin decreases the effect of furosemide
  • Gabapentin Gabapentin may increase the effect of fosphenytoin.
  • Gefitinib The CYP3A4 inducer, fosphenytoin, may decrease the serum concentration and therapeutic effects of gefitinib.
  • Hydrocortisone The enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, hydrocortisone.
  • Imatinib The hydantoin decreases the levels of imatinib
  • Irinotecan The hydantoin decreases the effect of irinotecan
  • Isoniazid Isoniazid may increase the effect of phenytoin in 20% of patients.
  • Itraconazole Phenytoin decreases the effect of itraconazole
  • L-DOPA The hydantoin decreases the effect of levodopa
  • Lamotrigine Phenytoin may reduce levels of lamotrigine
  • Levonorgestrel Phenytoin decreases the contraceptive effect
  • Lopinavir Levels of both drugs are affected
  • Lurasidone Concomitant therapy with a CYP3A4 inducer will decrease levels of lurasidone. Coadministration with lurasidone is contraindicated.
  • Mebendazole The hydantoin decreases the efficiency of mebendazole
  • Medroxyprogesterone Acetate The enzyme inducer, fosphenytoin, may decrease the effect of the hormone, medroxyprogesterone.
  • Megestrol acetate The enzyme inducer, fosphenytoin, may decrease the effect of the hormone, megestrol.
  • Mestranol This product may cause a slight decrease of contraceptive effect
  • Methadone The hydantoin decreases the effect of methadone
  • Methotrexate The antineoplasic agent decreases the effect of hydantoin
  • Methoxsalen The hydantoin decreases the effect of psoralene
  • Methylprednisolone The enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, methylprednisolone.
  • Metocurine Phenytoin decreases the effect of muscle relaxant
  • Metyrapone The combination renders the test invalid
  • Mexiletine The hydantoin decreases the effect of mexiletine
  • Midazolam Fosphenytoin may increase the metabolism of midazolam via CYP3A4.
  • Mirtazapine The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects
  • Mivacurium Phenytoin decreases the effect of muscle relaxant
  • Nisoldipine Phenytoin decreases the efficiency of nisoldipine
  • Norethindrone This product may cause a slight decrease of contraceptive effect
  • Omeprazole Omeprazole increases the effect of hydantoin
  • Oxcarbazepine Oxcarbazepine increases the effect of hydantoin
  • Oxtriphylline Decreased effect of both products
  • Oxyphenbutazone The NSAID, oxphenbutazone, may increase the hydantoin effect of fosphenytoin.
  • Pancuronium Phenytoin decreases the effect of muscle relaxant
  • Paramethasone The enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, paramethasone.
  • Phenylbutazone The NSAID, phenylbutazone, may increase the hydantoin effect of fosphenytoin.
  • Posaconazole Modifications of drug levels for both agents
  • Prednisolone The enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, prednisolone.
  • Prednisone The enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, prednisone.
  • Quetiapine Phenytoin decreases the effect of quetiapine
  • Quinestrol The enzyme inducer, fosphenytoin, decreases the effect of the hormone agent, quinestrol.
  • Quinidine The anticonvulsant, fosphenytoin, decreases the effect of quinidine.
  • Quinupristin This combination presents an increased risk of toxicity
  • Rifampicin Rifampin may decrease the effect of fosphenytoin.
  • Roflumilast Affects CYP3A4 metabolism, decreases level or effect of roflumilast.
  • Sertraline Sertraline increases the effect of hydantoin
  • Sirolimus The hydantoin decreases sirolimus levels
  • Sucralfate Sucralfate decreases the effect of hydantoin
  • Sulfadiazine The sulfonamide increases the effect of hydantoin
  • Sulfamethizole The sulfonamide increases the effect of hydantoin
  • Tacrolimus The hydantoin decreases the effect of tacrolimus
  • Telithromycin Fosphenytoin may decrease the plasma concentration of Telithromycin. Consider alternate therapy.
  • Temsirolimus Fosphenytoin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
  • Theophylline Decreased effect of both products
  • Thiotepa Possible increase in thiotepa levels
  • Ticlopidine Ticlopidine may decrease the metabolism and clearance of Fosphenytoin. Consider alternate therapy or monitor for adverse/toxic effects of Fosphenytoin if Ticlopidine is initiated, discontinued or dose changed.
  • Tolbutamide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Fosphenytoin. Consider alternate therapy or monitor for changes in Fosphenytoin therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
  • Topiramate Increased phenytoin/decreased topiramate
  • Tramadol Fosphenytoin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
  • Trazodone The CYP3A4 inducer, Fosphenytoin, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Fosphenytoin is initiated, discontinued or dose changed.
  • Tretinoin The strong CYP2C8 inducer, Fosphenytoin, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Fosphenytoin is initiated, discontinued or dose changed.
  • Triamcinolone The enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, triamcinolone.
  • Triazolam Fosphenytoin may increase the metabolism of triazolam via CYP3A4.
  • Trimethoprim Trimethoprim increases the effect of hydantoin
  • Trioxsalen The hydantoin decreases the effect of psoralene
  • Triprolidine The CNS depressants, Triprolidine and Fosphenytoin, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
  • Tubocurarine Phenytoin decreases the effect of muscle relaxant
  • Vandetanib Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • Vecuronium Phenytoin decreases the effect of muscle relaxant
  • Vigabatrin Vigabatrin decreases the effect of hydantoin
  • Vinblastine The antineoplasic agent decreases the effect of hydantoin
  • Voriconazole The hydantoin decreases the effect of voriconazole
  • Warfarin Increased hydantoin levels and risk of bleeding
Liều Lượng & Cách Dùng : Liquid - Intravenous
Liquid - Intravenous
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Cerebyx
  • Công ty :
    Sản phẩm biệt dược : Prodilantin
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01320
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=56339
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505168
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07840
ChemSpider
http://www.chemspider.com/Chemical-Structure.50839.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0071-4007-05
PharmGKB
http://www.pharmgkb.org/drug/PA164746820
Wikipedia
http://en.wikipedia.org/wiki/Fosphenytoin
RxList
http://www.rxlist.com/cgi/generic/fosphen.htm
Drugs.com
http://www.drugs.com/cdi/fosphenytoin.html
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