Gimeracil

DB09257

small molecule approved

Deskripsi

Gimeracil is an adjunct to antineoplastic therapy, used to increase the concentration and effect of the main active componets within chemotherapy regimens. Approved by the European Medicines Agency (EMA) in March 2011, Gimeracil is available in combination with DB03209 and DB09256 within the commercially available product "Teysuno". The main active ingredient in Teysuno is DB09256, a pro-drug of DB00544 (5-FU), which is a cytotoxic anti-metabolite drug that acts on rapidly dividing cancer cells. By mimicking a class of compounds called "pyrimidines" that are essential components of RNA and DNA, 5-FU is able to insert itself into strands of DNA and RNA, thereby halting the replication process necessary for continued cancer growth.

Gimeracil's main role within Teysuno is to prevent the breakdown of DB00544 (5-FU), which helps to maintin high enough concentrations for sustained effect against cancer cells L933. It functions by reversibly and selectively blocking the enzyme dihydropyrimidine dehydrogenase (DPD), which is involved in the degradation of 5-FU A31408. This allows higher concentrations of 5-FU to be achieved with a lower dose of tegafur, thereby also reducing toxic side effects.

Struktur Molekul 2D

Berat 145.54
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Following a single dose of Teysuno, T1/2 values ranged from 6.7 to 11.3 hours for tegafur, from 3.1 to 4.1 hours for gimeracil, and from 1.8 to 9.5 hours for oteracil [L933].
Volume Distribusi Although no intravenous data are available for Teysuno in humans, the volume of distribution could be roughly estimated from the apparent volume of distribution and urinary excretion data as 16 l/m2, 17 l/m2, and 23 l/m2 for tegafur, gimeracil and oteracil, respectively [L933].
Klirens (Clearance) -

Absorpsi

Mean 5-FU maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) values were approximately 3-fold higher after Teysuno administration than after administration of tegafur alone, despite a 16-fold lower Teysuno dose (50 mg of tegafur) compared to tegafur alone (800 mg), and are attributed to inhibition of DPD by gimeracil. Maximum plasma uracil concentration was observed at 4 hours, with a return to baseline levels within approximately 48 hours after dosing, indicating the reversibility of the DPD inhibition by gimeracil. After administration of a single dose of 50 mg Teysuno (expressed as tegafur content), median Tmax for Teysuno components tegafur, gimeracil, and oteracil was 0.5, 1.0, and 2.0 hours, respectively L933.

Metabolisme

Data metabolisme tidak tersedia.

Rute Eliminasi

Following a single dose of Teysuno, approximately 3.8% to 4.2% of administered tegafur, 65% to 72% of administered gimeracil, and 3.5% to 3.9% of administered oteracil were excreted unchanged in the urine L933.

Interaksi Makanan

2 Data
  • 1. Drink plenty of fluids. Drinking water is important to prevent dehydration when taking Teysuno.
  • 2. Take on an empty stomach. Take Teysuno at least 1 hour before or after eating.

Interaksi Obat

730 Data
Fluorouracil The serum concentration of Fluorouracil can be increased when it is combined with Gimeracil.
Flucytosine The serum concentration of Flucytosine can be increased when it is combined with Gimeracil.
Capecitabine The serum concentration of Capecitabine can be increased when it is combined with Gimeracil.
5-fluorouridine The serum concentration of 5-fluorouridine can be increased when it is combined with Gimeracil.
Uracil The serum concentration of Uracil can be increased when it is combined with Gimeracil.
Doxifluridine The serum concentration of Doxifluridine can be increased when it is combined with Gimeracil.
Cyclosporine Cyclosporine may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Icosapent Icosapent may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefotiam Cefotiam may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Mesalazine Mesalazine may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefmenoxime Cefmenoxime may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefmetazole Cefmetazole may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Pamidronic acid Pamidronic acid may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Tenofovir disoproxil Tenofovir disoproxil may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Indomethacin Indomethacin may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cidofovir Cidofovir may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefpiramide Cefpiramide may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Ceftazidime Ceftazidime may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Loracarbef Loracarbef may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefalotin Cefalotin may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Nabumetone Nabumetone may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Ketorolac Ketorolac may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Tenoxicam Tenoxicam may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Celecoxib Celecoxib may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefotaxime Cefotaxime may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Tolmetin Tolmetin may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Foscarnet Foscarnet may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Rofecoxib Rofecoxib may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Piroxicam Piroxicam may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Methotrexate Methotrexate may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cephalexin Cephalexin may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Fenoprofen Fenoprofen may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Valaciclovir Valaciclovir may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Valdecoxib Valdecoxib may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Diclofenac Diclofenac may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Sulindac Sulindac may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Bacitracin Bacitracin may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Amphotericin B Amphotericin B may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cephaloglycin Cephaloglycin may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Flurbiprofen Flurbiprofen may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Pentamidine Pentamidine may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Etodolac Etodolac may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Mefenamic acid Mefenamic acid may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Acyclovir Acyclovir may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Naproxen Naproxen may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Sulfasalazine Sulfasalazine may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Phenylbutazone Phenylbutazone may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Meloxicam Meloxicam may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Carprofen Carprofen may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefaclor Cefaclor may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Diflunisal Diflunisal may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Tacrolimus Tacrolimus may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Ceforanide Ceforanide may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Salicylic acid Salicylic acid may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Meclofenamic acid Meclofenamic acid may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Carboplatin Carboplatin may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Oxaprozin Oxaprozin may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Ketoprofen Ketoprofen may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Balsalazide Balsalazide may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Ibuprofen Ibuprofen may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefditoren Cefditoren may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Atazanavir Atazanavir may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Colistimethate Colistimethate may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefuroxime Cefuroxime may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefapirin Cefapirin may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefadroxil Cefadroxil may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefprozil Cefprozil may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Ceftriaxone Ceftriaxone may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Olsalazine Olsalazine may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Lumiracoxib Lumiracoxib may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefamandole Cefamandole may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefazolin Cefazolin may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefonicid Cefonicid may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefoperazone Cefoperazone may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefotetan Cefotetan may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefoxitin Cefoxitin may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Ceftizoxime Ceftizoxime may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefradine Cefradine may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Magnesium salicylate Magnesium salicylate may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Salsalate Salsalate may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Choline magnesium trisalicylate Choline magnesium trisalicylate may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefepime Cefepime may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefacetrile Cefacetrile may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Ceftibuten Ceftibuten may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cefpodoxime Cefpodoxime may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Antrafenine Antrafenine may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Aminophenazone Aminophenazone may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Antipyrine Antipyrine may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Tiaprofenic acid Tiaprofenic acid may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Lopinavir Lopinavir may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Etoricoxib Etoricoxib may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Hydrolyzed Cephalothin Hydrolyzed Cephalothin may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Cephalothin Group Cephalothin Group may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Oxyphenbutazone Oxyphenbutazone may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Latamoxef Latamoxef may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Nimesulide Nimesulide may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Benoxaprofen Benoxaprofen may decrease the excretion rate of Gimeracil which could result in a higher serum level.
Metamizole Metamizole may decrease the excretion rate of Gimeracil which could result in a higher serum level.

Target Protein

Dihydropyrimidine dehydrogenase [NADP(+)] DPYD

Referensi & Sumber

Artikel (PubMed)
  • PMID: 28927087
    Harada K, Ferdous T, Harada T, Takenawa T, Ueyama Y: Gimeracil enhances the antitumor effect of cisplatin in oral squamous cell carcinoma cells in vitro and in vivo. Oncol Lett. 2017 Sep;14(3):3349-3356. doi: 10.3892/ol.2017.6602. Epub 2017 Jul 18.

Contoh Produk & Brand

Produk: 5 • International brands: 0
Produk
  • Teysuno
    Capsule • - • Oral • EU • Approved
  • Teysuno
    Capsule • - • Oral • EU • Approved
  • Teysuno
    Capsule • - • Oral • EU • Approved
  • Teysuno
    Capsule • - • Oral • EU • Approved
  • Teysuno
    Capsule • - • Oral • EU • Approved

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