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药品详细

Rufinamide(卢非酰胺)

化学结构式图
中文名
卢非酰胺
英文名
Rufinamide
分子式
C10H8F2N4O
化学名
1-[(2,6-difluorophenyl)methyl]-1H-1,2,3-triazole-4-carboxamide
分子量
Average: 238.1935
Monoisotopic: 238.066617308
CAS号
106308-44-5
ATC分类
N03A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Rufinamide is a triazole derivative and an anticonvulsant medication to treat seizure disorders like Lennox-Gastuat syndrome, a form of childhood epilepsy. Clinical trials suggest its efficacy in the treatment of partial seizures.

生产厂家
  • Eisai inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Arroyo S: Rufinamide. Neurotherapeutics. 2007 Jan;4(1):155-62. Pubmed
  2. Hakimian S, Cheng-Hakimian A, Anderson GD, Miller JW: Rufinamide: a new anti-epileptic medication. Expert Opin Pharmacother. 2007 Aug;8(12):1931-40. Pubmed
  3. Rufinamide: CGP 33101, E 2080, RUF 331, Xilep. Drugs R D. 2005;6(4):249-52. Pubmed
  4. Wier HA, Cerna A, So TY: Rufinamide for pediatric patients with Lennox-Gastaut syndrome: a comprehensive overview. Paediatr Drugs. 2011 Apr 1;13(2):97-106. doi: 10.2165/11586920-000000000-00000. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes Not Available
Substructures Not Available
适应症
药理
Indication Adjunct therapy for treatment of seizures associated with Lennox-Gastaut syndrome.
Pharmacodynamics At high concentrations will inhibit action of mGluR5 subtype receptors thus preventing the production of glutamate.
Mechanism of action Rufinamide is a triazole derivative antiepileptic that prolongs the inactive state of voltage gated sodium channels thus stabilizing membranes, ultimately blocking the spread of partial seizure activity.
Absorption The oral suspension and tablet are bioequivalent on a mg per mg basis. Rufinamide is well absorbed but the rate is slow and the extent of absorption decreases as dose is increases. Based on urinary excretion, the extent of absorption was at least 85% following oral administration of a single dose of 600 mg rufinamide tablet under fed conditions. Bioavailability= 70%-85% (decreases with increasing doses); Tmax, fed and fasted states= 4-6 hours; Cmax, 10 mg/kg/day= 4.01 µL/mL; Cmax, 30mg/kg/day= 8.68 µL/mL; AUC (0h-12h), 10mg/kg/day= 37.8±47 µg·h/mL; AUC (0h-12h), 30mg/kg/day= 89.3±59 µg·h/mL.
Volume of distribution

Rufinamide was evenly distributed between erythrocytes and plasma. The apparent volume of distribution is dependent upon dose and varies with body surface area. The apparent volume of distribution was about 50 L at 3200 mg/day.
Volume of distribution is similar between adults and children and is non-linear.
Protein binding 26.3% - 34.8% with 90% binding to albumin (27%).
Metabolism
Rufinamide is extensively metabolized but has no active metabolites. Metabolism by carboxyesterases into inactive metabolite CGP 47292, a carboxylic acid derivative, via hydrolysis is the primary biotransformation pathway. A few minor additional metabolites were detected in urine, which appeared to be acyl-glucuronides of CGP 47292. The cytochrome P450 enzyme system or glutathiones are not involved with the metabolism of rufinamide. Rufinamide is a weak inhibitor of CYP 2E1. Rufinamide is a weak inducer of CYP 3A4 enzymes.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Rufinamide
    		CGP 47292 Details
    Route of elimination Renally (91%; 66% as CGP 47292, 2% as unchanged drug) and fecally (9%) eliminated.
    Half life Elimination half-life, healthy subjects and patients with epilepsy = 6-10 hours.
    Clearance Not Available
    Toxicity The most commonly observed adverse reactions (≥10% and greater than placebo) were headache, dizziness, fatigue, somnolence, and nausea.
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    water solubility Insoluble FDA label
    logP 0.835 MSDS
    Predicted Properties
    Property Value Source
    water solubility 6.42e-01 g/l ALOGPS
    logP 0.95 ALOGPS
    logP 1.27 ChemAxon
    logS -2.6 ALOGPS
    pKa (strongest acidic) 12.69 ChemAxon
    pKa (strongest basic) -1.1 ChemAxon
    physiological charge 0 ChemAxon
    hydrogen acceptor count 3 ChemAxon
    hydrogen donor count 1 ChemAxon
    polar surface area 73.8 ChemAxon
    rotatable bond count 3 ChemAxon
    refractivity 67.07 ChemAxon
    polarizability 20.42 ChemAxon
    药物相互作用
    Drug Interaction
    Carbamazepine Decrease concentration of rufinamide thus monitor therapy
    Ethinyl Estradiol Rufinamide decreases plasma concentrations of ethinyl estradiol, thus consider therapy modification
    Norethindrone Rufinamide decreases plasma concentrations of norethindrone, thus consider therapy modification
    Phenobarbital Increases clearance of rufinamide thus decreasing plasma concentration of rufinamide.
    Phenytoin Increases clearance of rufinamide thus decreasing plasma concentration of rufinamide.
    Primidone Increases clearance of rufinamide thus decreasing plasma concentration of rufinamide.
    Valproic Acid Valproic acid may increase the therapeutic/toxic effects of Rufinamide. Consider alternate therapy or monitor for changes in Rufinamide serum concentrations, therapeutic and adverse effects if Valproic acid is initiated, discontinued or dose changed. Decreases clearance of rufinamide and is a selective inhibitor of human carboxylesterase thus increasing serum concentrations.
    食物相互作用
    • Food increases plasma concentrations of rufinamide and slightly decreases half-life (by 3%)

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