Peringatan Keamanan

Lethal Dose, acute, oral, rat = 100 mg/kg;
Lethal Dose, chronic, oral, rat = 5.1 mg/kg/day, 90-day;
Most common adverse effects that lead to discontinuation of therapy include dizziness and somnolence.

Ezogabine

DB04953

small molecule approved investigational

Deskripsi

Ezogabine (D23129) is a close structural analog of the centrally acting analgesic flupitrine. It is a neuronal potassium channel opener being developed as a first-in-class antiepileptic drug (AED) and is currently being studied in Phase 3 trials as an adjunctive treatment for partial-onset seizures in adult patients with refractory epilepsy. FDA approved in June 10, 2011 under the name of ezogabine.

Struktur Molekul 2D

Berat 303.3314
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Terminal half-life = 7.5 hours
Volume Distribusi 8.7 L/kg
Klirens (Clearance) 0.58 - 0.76 L/h·kg. Clearance may differ between ethnic groups with Black Americans having 20% lower clearance than Caucasian Americans.

Absorpsi

Rapidly absorbed and distributed, with an absolute oral bioavailability of 60%. Pharmacokinetics of ezogabine suggest first-order kinetics. Tmax, single oral dose = 30-120 minutes; Time to steady state = 3 days

Metabolisme

Ezogabine is metabolized exclusively via phase II hepatic N-glucurodination and acetylation. N-glucurodination is the major metabolic pathway of the two and form two major N-glucuronide metabolites. The enzymes involved are UGT1A1, 1A9, 1A4, and 1A3. However, the product of the N-acetyl pathway is a weak, active metabolite referred to as NAMR. The enzyme that is involved in the N-acetyl pathway is called N-acetyltransferase 2. The pharmacokinetics of NAMR and ezogabine are similar. The cytochrome P450 enzyme system is not involved with the metabolism of ezogabine.

Rute Eliminasi

Urine (85%, 36% of total dose as unchanged drug, 18% of total dose as NAMR) and feces (14%, 3% of total dose as unchanged drug)

Interaksi Makanan

1 Data
  • 1. Take with or without food. High-fat meals alter drug absorption, but not to a clinically significant extent.

Interaksi Obat

1647 Data
Buprenorphine Ezogabine may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
Doxylamine Doxylamine may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
Dronabinol Dronabinol may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
Droperidol Droperidol may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
Hydrocodone Ezogabine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
Magnesium sulfate The therapeutic efficacy of Ezogabine can be increased when used in combination with Magnesium sulfate.
Methotrimeprazine Ezogabine may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
Metyrosine Ezogabine may increase the sedative activities of Metyrosine.
Minocycline Minocycline may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
Mirtazapine Ezogabine may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
Nabilone Nabilone may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
Orphenadrine Ezogabine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
Paraldehyde Ezogabine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
Perampanel Perampanel may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
Pramipexole Ezogabine may increase the sedative activities of Pramipexole.
Ropinirole Ezogabine may increase the sedative activities of Ropinirole.
Rotigotine Ezogabine may increase the sedative activities of Rotigotine.
Rufinamide The risk or severity of adverse effects can be increased when Rufinamide is combined with Ezogabine.
Sodium oxybate Ezogabine may increase the central nervous system depressant (CNS depressant) activities of Sodium oxybate.
Suvorexant Ezogabine may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
Tapentadol Tapentadol may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
Thalidomide Ezogabine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
Zolpidem Ezogabine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Mefloquine The therapeutic efficacy of Ezogabine can be decreased when used in combination with Mefloquine.
Mianserin The therapeutic efficacy of Ezogabine can be decreased when used in combination with Mianserin.
Orlistat Orlistat can cause a decrease in the absorption of Ezogabine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Phenytoin The serum concentration of Ezogabine can be decreased when it is combined with Phenytoin.
Fosphenytoin The serum concentration of Ezogabine can be decreased when it is combined with Fosphenytoin.
Topotecan Ezogabine may increase the excretion rate of Topotecan which could result in a lower serum level and potentially a reduction in efficacy.
Methadone The risk or severity of adverse effects can be increased when Methadone is combined with Ezogabine.
Lamotrigine The serum concentration of Lamotrigine can be decreased when it is combined with Ezogabine.
Carbamazepine The serum concentration of Ezogabine can be decreased when it is combined with Carbamazepine.
Nelfinavir The metabolism of Ezogabine can be increased when combined with Nelfinavir.
Zidovudine The metabolism of Ezogabine can be increased when combined with Zidovudine.
Ritonavir The metabolism of Ezogabine can be increased when combined with Ritonavir.
Efavirenz The metabolism of Ezogabine can be increased when combined with Efavirenz.
Primidone The metabolism of Ezogabine can be increased when combined with Primidone.
Tipranavir The metabolism of Ezogabine can be increased when combined with Tipranavir.
Rifampin The metabolism of Ezogabine can be increased when combined with Rifampicin.
Phenobarbital The metabolism of Ezogabine can be increased when combined with Phenobarbital.
Testosterone propionate The metabolism of Ezogabine can be increased when combined with Testosterone propionate.
Tetracosactide The risk or severity of liver damage can be increased when Tetracosactide is combined with Ezogabine.
Azelastine Ezogabine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
Brimonidine Brimonidine may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
Fluvoxamine The risk or severity of adverse effects can be increased when Ezogabine is combined with Fluvoxamine.
Duloxetine The risk or severity of adverse effects can be increased when Ezogabine is combined with Duloxetine.
Paroxetine The risk or severity of adverse effects can be increased when Ezogabine is combined with Paroxetine.
Sertraline The risk or severity of adverse effects can be increased when Ezogabine is combined with Sertraline.
Sibutramine The risk or severity of adverse effects can be increased when Ezogabine is combined with Sibutramine.
Nefazodone The risk or severity of adverse effects can be increased when Ezogabine is combined with Nefazodone.
Zimelidine The risk or severity of adverse effects can be increased when Ezogabine is combined with Zimelidine.
Dapoxetine The risk or severity of adverse effects can be increased when Ezogabine is combined with Dapoxetine.
Milnacipran The risk or severity of adverse effects can be increased when Ezogabine is combined with Milnacipran.
Desvenlafaxine The risk or severity of adverse effects can be increased when Ezogabine is combined with Desvenlafaxine.
Seproxetine The risk or severity of adverse effects can be increased when Ezogabine is combined with Seproxetine.
Levomilnacipran Ezogabine may decrease the excretion rate of Levomilnacipran which could result in a higher serum level.
Indalpine The risk or severity of adverse effects can be increased when Ezogabine is combined with Indalpine.
Ritanserin The risk or severity of adverse effects can be increased when Ezogabine is combined with Ritanserin.
Alaproclate The risk or severity of adverse effects can be increased when Ezogabine is combined with Alaproclate.
Citalopram The risk or severity of QTc prolongation can be increased when Ezogabine is combined with Citalopram.
Escitalopram The risk or severity of adverse effects can be increased when Ezogabine is combined with Escitalopram.
Benzatropine The risk or severity of QTc prolongation can be increased when Benzatropine is combined with Ezogabine.
Buclizine The risk or severity of QTc prolongation can be increased when Buclizine is combined with Ezogabine.
Hyoscyamine The risk or severity of QTc prolongation can be increased when Hyoscyamine is combined with Ezogabine.
Cyproheptadine The risk or severity of CNS depression can be increased when Cyproheptadine is combined with Ezogabine.
Nortriptyline The risk or severity of CNS depression can be increased when Nortriptyline is combined with Ezogabine.
Amoxapine The risk or severity of CNS depression can be increased when Amoxapine is combined with Ezogabine.
Nicardipine The risk or severity of QTc prolongation can be increased when Nicardipine is combined with Ezogabine.
Propiomazine The risk or severity of CNS depression can be increased when Propiomazine is combined with Ezogabine.
Propantheline Propantheline may decrease the excretion rate of Ezogabine which could result in a higher serum level.
Dicyclomine Dicyclomine may decrease the excretion rate of Ezogabine which could result in a higher serum level.
Maprotiline The risk or severity of CNS depression can be increased when Maprotiline is combined with Ezogabine.
Tolterodine The risk or severity of QTc prolongation can be increased when Tolterodine is combined with Ezogabine.
Flavoxate Flavoxate may decrease the excretion rate of Ezogabine which could result in a higher serum level.
Tiotropium Tiotropium may decrease the excretion rate of Ezogabine which could result in a higher serum level.
Solifenacin The risk or severity of QTc prolongation can be increased when Solifenacin is combined with Ezogabine.
Pizotifen The risk or severity of CNS depression can be increased when Ezogabine is combined with Pizotifen.
Fesoterodine Ezogabine may decrease the excretion rate of Fesoterodine which could result in a higher serum level.
Aclidinium Ezogabine may decrease the excretion rate of Aclidinium which could result in a higher serum level.
Trimebutine The risk or severity of QTc prolongation can be increased when Ezogabine is combined with Trimebutine.
Dosulepin The risk or severity of CNS depression can be increased when Ezogabine is combined with Dosulepin.
Imidafenacin Ezogabine may decrease the excretion rate of Imidafenacin which could result in a higher serum level.
Propiverine Ezogabine may decrease the excretion rate of Propiverine which could result in a higher serum level.
Amitriptyline The risk or severity of CNS depression can be increased when Amitriptyline is combined with Ezogabine.
Imipramine The risk or severity of CNS depression can be increased when Imipramine is combined with Ezogabine.
Doxepin The risk or severity of CNS depression can be increased when Doxepin is combined with Ezogabine.
Desipramine The risk or severity of CNS depression can be increased when Desipramine is combined with Ezogabine.
Zopiclone The risk or severity of adverse effects can be increased when Ezogabine is combined with Zopiclone.
Ethanol The serum concentration of Ezogabine can be increased when it is combined with Ethanol.
Leuprolide The risk or severity of QTc prolongation can be increased when Ezogabine is combined with Leuprolide.
Goserelin The risk or severity of QTc prolongation can be increased when Ezogabine is combined with Goserelin.
Erythromycin The risk or severity of QTc prolongation can be increased when Ezogabine is combined with Erythromycin.
Azithromycin The risk or severity of QTc prolongation can be increased when Ezogabine is combined with Azithromycin.
Moxifloxacin The risk or severity of QTc prolongation can be increased when Ezogabine is combined with Moxifloxacin.
Ranolazine The risk or severity of QTc prolongation can be increased when Ezogabine is combined with Ranolazine.
Sulfisoxazole The risk or severity of QTc prolongation can be increased when Ezogabine is combined with Sulfisoxazole.
Diltiazem The risk or severity of QTc prolongation can be increased when Ezogabine is combined with Diltiazem.
Nimodipine The risk or severity of QTc prolongation can be increased when Ezogabine is combined with Nimodipine.
Oxaliplatin The risk or severity of QTc prolongation can be increased when Oxaliplatin is combined with Ezogabine.
Ciprofloxacin The risk or severity of QTc prolongation can be increased when Ezogabine is combined with Ciprofloxacin.

Target Protein

Potassium voltage-gated channel subfamily KQT member 3 KCNQ3
Potassium voltage-gated channel subfamily KQT member 2 KCNQ2
Potassium voltage-gated channel subfamily KQT member 4 KCNQ4
Potassium voltage-gated channel subfamily KQT member 5 KCNQ5

Referensi & Sumber

Artikel (PubMed)
  • PMID: 17199031
    Porter RJ, Nohria V, Rundfeldt C: Retigabine. Neurotherapeutics. 2007 Jan;4(1):149-54.
  • PMID: 12545144
    Hermann R, Ferron GM, Erb K, Knebel N, Ruus P, Paul J, Richards L, Cnota HP, Troy S: Effects of age and sex on the disposition of retigabine. Clin Pharmacol Ther. 2003 Jan;73(1):61-70.
  • PMID: 12698305
    Hermann R, Knebel NG, Niebch G, Richards L, Borlak J, Locher M: Pharmacokinetic interaction between retigabine and lamotrigine in healthy subjects. Eur J Clin Pharmacol. 2003 Apr;58(12):795-802. Epub 2003 Feb 28.
  • PMID: 15007538
    Dost R, Rostock A, Rundfeldt C: The anti-hyperalgesic activity of retigabine is mediated by KCNQ potassium channel activation. Naunyn Schmiedebergs Arch Pharmacol. 2004 Apr;369(4):382-90. Epub 2004 Mar 9.
  • PMID: 15158023
    Mikkelsen JD: The KCNQ channel activator retigabine blocks haloperidol-induced c-Fos expression in the striatum of the rat. Neurosci Lett. 2004 May 27;362(3):240-3.
  • PMID: 15277926
    Punke MA, Friederich P: Retigabine stimulates human KCNQ2/Q3 channels in the presence of bupivacaine. Anesthesiology. 2004 Aug;101(2):430-8.
  • PMID: 15662042
    Wuttke TV, Seebohm G, Bail S, Maljevic S, Lerche H: The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate. Mol Pharmacol. 2005 Apr;67(4):1009-17. Epub 2005 Jan 20.
  • PMID: 16034707
    Fatope MO: Retigabine (ASTA Medica). IDrugs. 2001 Jan;4(1):93-8.
Menampilkan 8 dari 10 artikel.

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Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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