Peringatan Keamanan

The most common adverse effects (>20%) for cobimetinib are diarrhea, photosensitivity reactions, nausea, fever and vomiting.

Cobimetinib

DB05239

small molecule approved investigational

Deskripsi

Cobimetinib is an orally active, potent and highly selective small molecule inhibiting mitogen-activated protein kinase kinase 1 (MAP2K1 or MEK1), and central components of the RAS/RAF/MEK/ERK signal transduction pathway. It has been approved in Switzerland and the US, in combination with vemurafenib for the treatment of patients with unresectable or metastatic BRAF V600 mutation-positive melanoma.

Struktur Molekul 2D

Berat 531.318
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) Following oral administration of COTELLIC 60 mg once daily in cancer patients, the mean elimination half-life (t1/2) was 44 (range: 23–70) hours.[L43717]
Volume Distribusi The estimated apparent volume of distribution was 806 L in cancer patients based on a population PK analysis.[L43717]
Klirens (Clearance) Following oral administration of COTELLIC 60 mg once daily in cancer patients, the mean apparent clearance (CL/F) was 13.8 L/h (61% CV).[L43717]

Absorpsi

Following oral dosing of 60 mg once daily in cancer patients, the median time to achieve peak plasma levels (Tmax) was 2.4 (range:1–24) hours, geometric mean steady-state AUC0-24h was 4340 ng?h/mL (61% CV) and Cmax was 273 ng/mL (60% CV). The absolute bioavailability of COTELLIC was 46% (90% CI: 40%, 53%) in healthy subjects. A high?fat meal (comprised of approximately 150 calories from protein, 250 calories from carbohydrate, and 500–600 calories from fat) had no effect on cobimetinib AUC and Cmax after a single 20 mg COTELLIC was administered to healthy subjects.L43717

Metabolisme

Cobimetinib is mainly metabolized via CYP3A oxidation and UGT2B7 glucuronidation with no major metabolites formed.L43717

Rute Eliminasi

Following oral administration of a single 20 mg radiolabeled cobimetinib dose, 76% of the dose was recovered in the feces (with 6.6% as unchanged drug) and 17.8% of the dose was recovered in the urine (with 1.6% as unchanged drug).L43717

Interaksi Makanan

3 Data
  • 1. Avoid grapefruit products. Grapefruit inhibits the metabolism of cobimetinib through the CYP3A4 pathway and, therefore, may increase serum levels of cobimetinib.
  • 2. Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce serum levels of cobimetinib.
  • 3. Take with or without food. Cobimetinib bioavailability is unaffected by food.

Interaksi Obat

678 Data
Modafinil The metabolism of Cobimetinib can be increased when combined with Modafinil.
Armodafinil The metabolism of Cobimetinib can be increased when combined with Armodafinil.
Ranolazine The serum concentration of Cobimetinib can be increased when it is combined with Ranolazine.
Phenytoin The serum concentration of Cobimetinib can be decreased when it is combined with Phenytoin.
Fosphenytoin The serum concentration of Cobimetinib can be decreased when it is combined with Fosphenytoin.
Metreleptin The metabolism of Cobimetinib can be increased when combined with Metreleptin.
Lumacaftor The serum concentration of Cobimetinib can be decreased when it is combined with Lumacaftor.
Isavuconazole The metabolism of Cobimetinib can be decreased when combined with Isavuconazole.
Fluconazole The metabolism of Cobimetinib can be decreased when combined with Fluconazole.
Erythromycin The metabolism of Cobimetinib can be decreased when combined with Erythromycin.
Isradipine The metabolism of Cobimetinib can be decreased when combined with Isradipine.
Diltiazem The metabolism of Cobimetinib can be decreased when combined with Diltiazem.
Haloperidol The metabolism of Cobimetinib can be decreased when combined with Haloperidol.
Nicardipine The metabolism of Cobimetinib can be decreased when combined with Nicardipine.
Verapamil The metabolism of Cobimetinib can be decreased when combined with Verapamil.
Primaquine The metabolism of Cobimetinib can be decreased when combined with Primaquine.
Miconazole The metabolism of Cobimetinib can be decreased when combined with Miconazole.
Zimelidine The metabolism of Cobimetinib can be decreased when combined with Zimelidine.
Simeprevir The metabolism of Cobimetinib can be decreased when combined with Simeprevir.
Isavuconazonium The metabolism of Cobimetinib can be decreased when combined with Isavuconazonium.
Crizotinib The metabolism of Cobimetinib can be decreased when combined with Crizotinib.
Linagliptin The metabolism of Cobimetinib can be decreased when combined with Linagliptin.
Netupitant The metabolism of Cobimetinib can be decreased when combined with Netupitant.
Venetoclax The metabolism of Cobimetinib can be decreased when combined with Venetoclax.
Clozapine The metabolism of Cobimetinib can be decreased when combined with Clozapine.
Ciprofloxacin The metabolism of Cobimetinib can be decreased when combined with Ciprofloxacin.
Fluvoxamine The metabolism of Cobimetinib can be decreased when combined with Fluvoxamine.
Voriconazole The metabolism of Cobimetinib can be decreased when combined with Voriconazole.
Ziprasidone The metabolism of Cobimetinib can be decreased when combined with Ziprasidone.
Isoniazid The metabolism of Cobimetinib can be decreased when combined with Isoniazid.
Danazol The metabolism of Cobimetinib can be decreased when combined with Danazol.
Fusidic acid The metabolism of Cobimetinib can be decreased when combined with Fusidic acid.
Milnacipran The metabolism of Cobimetinib can be decreased when combined with Milnacipran.
Desvenlafaxine The metabolism of Cobimetinib can be decreased when combined with Desvenlafaxine.
Nilvadipine The metabolism of Cobimetinib can be decreased when combined with Nilvadipine.
Seproxetine The metabolism of Cobimetinib can be decreased when combined with Seproxetine.
Indalpine The metabolism of Cobimetinib can be decreased when combined with Indalpine.
Barnidipine The metabolism of Cobimetinib can be decreased when combined with Barnidipine.
Benidipine The metabolism of Cobimetinib can be decreased when combined with Benidipine.
Fosnetupitant The metabolism of Cobimetinib can be decreased when combined with Fosnetupitant.
Cyclosporine The metabolism of Cobimetinib can be decreased when combined with Cyclosporine.
Aprepitant The metabolism of Cobimetinib can be decreased when combined with Aprepitant.
Dronedarone The metabolism of Cobimetinib can be decreased when combined with Dronedarone.
Berotralstat The metabolism of Cobimetinib can be decreased when combined with Berotralstat.
Vemurafenib The serum concentration of Cobimetinib can be increased when it is combined with Vemurafenib.
Apalutamide The serum concentration of Cobimetinib can be decreased when it is combined with Apalutamide.
Pitolisant The serum concentration of Cobimetinib can be decreased when it is combined with Pitolisant.
Valsartan The excretion of Valsartan can be decreased when combined with Cobimetinib.
Ouabain The excretion of Ouabain can be decreased when combined with Cobimetinib.
Cholecystokinin The excretion of Cholecystokinin can be decreased when combined with Cobimetinib.
Caspofungin The excretion of Caspofungin can be decreased when combined with Cobimetinib.
Conjugated estrogens The excretion of Conjugated estrogens can be decreased when combined with Cobimetinib.
Atorvastatin The excretion of Atorvastatin can be decreased when combined with Cobimetinib.
Taurocholic acid The excretion of Taurocholic acid can be decreased when combined with Cobimetinib.
Bempedoic acid The excretion of Bempedoic acid can be decreased when combined with Cobimetinib.
Fluvastatin The excretion of Fluvastatin can be decreased when combined with Cobimetinib.
Levothyroxine The serum concentration of Cobimetinib can be decreased when it is combined with Levothyroxine.
Trazodone The serum concentration of Cobimetinib can be decreased when it is combined with Trazodone.
Dexamethasone acetate The serum concentration of Cobimetinib can be decreased when it is combined with Dexamethasone acetate.
Reserpine The serum concentration of Cobimetinib can be increased when it is combined with Reserpine.
Sorafenib The serum concentration of Cobimetinib can be increased when it is combined with Sorafenib.
Loxapine The serum concentration of Cobimetinib can be increased when it is combined with Loxapine.
Quinine The serum concentration of Cobimetinib can be increased when it is combined with Quinine.
Toremifene The serum concentration of Cobimetinib can be increased when it is combined with Toremifene.
Tamoxifen The serum concentration of Cobimetinib can be increased when it is combined with Tamoxifen.
Mifepristone The serum concentration of Cobimetinib can be decreased when it is combined with Mifepristone.
Zonisamide The serum concentration of Cobimetinib can be increased when it is combined with Zonisamide.
Carvedilol The serum concentration of Cobimetinib can be increased when it is combined with Carvedilol.
Propafenone The serum concentration of Cobimetinib can be increased when it is combined with Propafenone.
Lapatinib The serum concentration of Cobimetinib can be increased when it is combined with Lapatinib.
Paliperidone The serum concentration of Cobimetinib can be increased when it is combined with Paliperidone.
Mibefradil The serum concentration of Cobimetinib can be increased when it is combined with Mibefradil.
Biricodar The serum concentration of Cobimetinib can be increased when it is combined with Biricodar.
Elacridar The serum concentration of Cobimetinib can be increased when it is combined with Elacridar.
Flibanserin The serum concentration of Cobimetinib can be increased when it is combined with Flibanserin.
Vandetanib The serum concentration of Cobimetinib can be increased when it is combined with Vandetanib.
Zosuquidar The serum concentration of Cobimetinib can be increased when it is combined with Zosuquidar.
Tariquidar The serum concentration of Cobimetinib can be increased when it is combined with Tariquidar.
Brefeldin A The serum concentration of Cobimetinib can be increased when it is combined with Brefeldin A.
Ivacaftor The serum concentration of Cobimetinib can be increased when it is combined with Ivacaftor.
Regorafenib The serum concentration of Cobimetinib can be increased when it is combined with Regorafenib.
Ponatinib The serum concentration of Cobimetinib can be increased when it is combined with Ponatinib.
Canagliflozin The serum concentration of Cobimetinib can be increased when it is combined with Canagliflozin.
Afatinib The serum concentration of Cobimetinib can be increased when it is combined with Afatinib.
Ledipasvir The serum concentration of Cobimetinib can be increased when it is combined with Ledipasvir.
Vorapaxar The serum concentration of Cobimetinib can be increased when it is combined with Vorapaxar.
Suvorexant The serum concentration of Cobimetinib can be increased when it is combined with Suvorexant.
Palbociclib The serum concentration of Cobimetinib can be increased when it is combined with Palbociclib.
Daclatasvir The serum concentration of Cobimetinib can be increased when it is combined with Daclatasvir.
Niguldipine The serum concentration of Cobimetinib can be increased when it is combined with Niguldipine.
Rolapitant The serum concentration of Cobimetinib can be increased when it is combined with Rolapitant.
Asunaprevir The serum concentration of Cobimetinib can be increased when it is combined with Asunaprevir.
Velpatasvir The serum concentration of Cobimetinib can be increased when it is combined with Velpatasvir.
Neratinib The serum concentration of Cobimetinib can be increased when it is combined with Neratinib.
Valspodar The serum concentration of Cobimetinib can be increased when it is combined with Valspodar.
Dacomitinib The serum concentration of Cobimetinib can be increased when it is combined with Dacomitinib.
Glasdegib The serum concentration of Cobimetinib can be increased when it is combined with Glasdegib.
Voxilaprevir The serum concentration of Cobimetinib can be increased when it is combined with Voxilaprevir.
Sarecycline The serum concentration of Cobimetinib can be increased when it is combined with Sarecycline.
Rucaparib The metabolism of Cobimetinib can be decreased when combined with Rucaparib.

Target Protein

Dual specificity mitogen-activated protein kinase kinase 1 MAP2K1

Referensi & Sumber

Artikel (PubMed)
  • PMID: 26452567
    Garnock-Jones KP: Cobimetinib: First Global Approval. Drugs. 2015 Oct;75(15):1823-30. doi: 10.1007/s40265-015-0477-8.
  • PMID: 26365290
    Han K, Jin JY, Marchand M, Eppler S, Choong N, Hack SP, Tikoo N, Bruno R, Dresser M, Musib L, Budha NR: Population pharmacokinetics and dosing implications for cobimetinib in patients with solid tumors. Cancer Chemother Pharmacol. 2015 Nov;76(5):917-24. doi: 10.1007/s00280-015-2862-0. Epub 2015 Sep 13.
  • PMID: 26384788
    Singh A, Ruan Y, Tippett T, Narendran A: Targeted inhibition of MEK1 by cobimetinib leads to differentiation and apoptosis in neuroblastoma cells. J Exp Clin Cancer Res. 2015 Sep 18;34:104. doi: 10.1186/s13046-015-0222-x.
  • PMID: 26730180
    Tran KA, Cheng MY, Mitra A, Ogawa H, Shi VY, Olney LP, Kloxin AM, Maverakis E: MEK inhibitors and their potential in the treatment of advanced melanoma: the advantages of combination therapy. Drug Des Devel Ther. 2015 Dec 21;10:43-52. doi: 10.2147/DDDT.S93545. eCollection 2016.
  • PMID: 26451002
    Takahashi RH, Choo EF, Ma S, Wong S, Halladay J, Deng Y, Rooney I, Gates M, Hop CE, Khojasteh SC, Dresser MJ, Musib L: Absorption, Metabolism, Excretion, and the Contribution of Intestinal Metabolism to the Oral Disposition of 14CCobimetinib, a MEK Inhibitor, in Humans. Drug Metab Dispos. 2016 Jan;44(1):28-39. doi: 10.1124/dmd.115.066282. Epub 2015 Oct 8.

Contoh Produk & Brand

Produk: 4 • International brands: 0
Produk
  • Cotellic
    Tablet, film coated • 20 mg • Oral • EU • Approved
  • Cotellic
    Tablet, film coated • 20 mg/1 • Oral • US • Approved
  • Cotellic
    Tablet, film coated • 20 mg/1mg • Oral • US • Approved
  • Cotellic
    Tablet • 20 mg • Oral • Canada • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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