Peringatan Keamanan

TAS-102 is a cytotoxic drug, therefore this combination drug can cause myelosupression, including neutropenia, anemia, thrombocytopenia, and febrile neutropenia. According to pre-clinical studies, TAS-102 presents also embryo-fetal toxicity.A31254

Tipiracil

DB09343

small molecule approved investigational

Deskripsi

Tipiracil is a thymidine phosphorylase inhibitor. It is used in combination with trifluridine, in a ratio of 1:0.5, to form TAS-102. The main function of Tipiracil in TAS-102 is to increase trifluridine bioavailability by inhibiting its catabolism.A31255 TAS-102 is indicated for the treatment of metastatic colorectal cancer which has been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, or with an anti-VEGF or anti-EGFR therapy.A31254

Struktur Molekul 2D

Berat 242.662
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) After administration of LONSURF 35 mg/m<sup>2</sup>, the mean elimination and steady-state half-life (t<sub>1/2</sub>) of tipiracil was 2.1 hours and 2.4 hours respectively.[L47676]
Volume Distribusi Following a single dose of LONSURF (35 mg/m<sup>2</sup>) in patients with advanced solid tumours, the apparent volume of distribution (Vd/F) for tipiracil hydrochloride was 333 L.[L47681]
Klirens (Clearance) Following a single dose of LONSURF (35 mg/m<sup>2</sup>) in patients with advanced solid tumours, the oral clearance (CL/F) for tipiracil hydrochloride was 109 L/hr.[L47681]

Absorpsi

Absorption of tipiracil is suggested to be done by the gastrointestinal tract. A31261 Administration of a single 35 mg/m2 dose of TAS-102 containing tipiracil and trifluridine, generates the absoprtion rates of tipiracil of AUC 301 ng h/ml, maximum observed plasma concentration (Cmax) 69 ng/ml and time for maximum observed plasma concentration (Tmax) 3 h. A31259 The consumption of a high-fat and high-calorie meal can decrease Cmax and AUC by 40%.A31260 A standardized high-fat, high-calorie meal decreased tipiracil Cmax and AUC by approximately 40% in patients with cancer following administration of a single dose of LONSURF 35 mg.L47681

Metabolisme

Tipiracil does not undergo much metabolism upon first pass. It is not metabolized by the liver or hepatocytes, nor by the cytochrome P450 enzymes. The only tipiracil-derived metabolite found in very small quantities in human plasma, urine or faeces is 6-hydroxymethyluracil (6-HMU) which is not unique of tipiracil. This metabolite is though to be formed either by enterobacterial metabolism. In plasma, this two metabolites can be found in a proportion of tipiracil 53.1% and 6-HMU 30.9%.A31261

Rute Eliminasi

After single oral administration of LONSURF (60 mg) with 14C-tipiracil hydrochloride, recovered radioactivity was 77% of the dose, which consisted of 27% urinary excretion and 50% fecal excretion. Tipiracil was the major component and 6-HMU was the major metabolite in urine and feces.L47676

Interaksi Makanan

1 Data
  • 1. Take with food.

Interaksi Obat

70 Data
Choline The excretion of Tipiracil can be decreased when combined with Choline.
Thiamine The excretion of Tipiracil can be decreased when combined with Thiamine.
Nicotine The excretion of Tipiracil can be decreased when combined with Nicotine.
Ranolazine The excretion of Tipiracil can be decreased when combined with Ranolazine.
Metoprolol The excretion of Tipiracil can be decreased when combined with Metoprolol.
Disopyramide The excretion of Tipiracil can be decreased when combined with Disopyramide.
Aminohippuric acid The excretion of Tipiracil can be decreased when combined with Aminohippuric acid.
Grepafloxacin The excretion of Tipiracil can be decreased when combined with Grepafloxacin.
Norepinephrine The excretion of Tipiracil can be decreased when combined with Norepinephrine.
Progesterone The excretion of Tipiracil can be decreased when combined with Progesterone.
Imipramine The excretion of Tipiracil can be decreased when combined with Imipramine.
Quinine The excretion of Tipiracil can be decreased when combined with Quinine.
Cimetidine The excretion of Tipiracil can be decreased when combined with Cimetidine.
Cisplatin The excretion of Tipiracil can be decreased when combined with Cisplatin.
Guanidine The excretion of Tipiracil can be decreased when combined with Guanidine.
Lamotrigine The excretion of Tipiracil can be decreased when combined with Lamotrigine.
Propranolol The excretion of Tipiracil can be decreased when combined with Propranolol.
Amiloride The excretion of Tipiracil can be decreased when combined with Amiloride.
Imatinib The excretion of Tipiracil can be decreased when combined with Imatinib.
Flurazepam The excretion of Tipiracil can be decreased when combined with Flurazepam.
Clopidogrel The excretion of Tipiracil can be decreased when combined with Clopidogrel.
Estradiol The excretion of Tipiracil can be decreased when combined with Estradiol.
Ranitidine The excretion of Tipiracil can be decreased when combined with Ranitidine.
Quinidine The excretion of Tipiracil can be decreased when combined with Quinidine.
Phenformin The excretion of Tipiracil can be decreased when combined with Phenformin.
Amantadine The excretion of Tipiracil can be decreased when combined with Amantadine.
Dinoprostone The excretion of Tipiracil can be decreased when combined with Dinoprostone.
Phenoxybenzamine The excretion of Tipiracil can be decreased when combined with Phenoxybenzamine.
Famotidine The excretion of Tipiracil can be decreased when combined with Famotidine.
Dopamine The excretion of Tipiracil can be decreased when combined with Dopamine.
Probenecid The excretion of Tipiracil can be decreased when combined with Probenecid.
Procainamide The excretion of Tipiracil can be decreased when combined with Procainamide.
Diphenhydramine The excretion of Tipiracil can be decreased when combined with Diphenhydramine.
Quinacrine The excretion of Tipiracil can be decreased when combined with Quinacrine.
Chlorpheniramine The excretion of Tipiracil can be decreased when combined with Chlorpheniramine.
Amiodarone The excretion of Tipiracil can be decreased when combined with Amiodarone.
Desipramine The excretion of Tipiracil can be decreased when combined with Desipramine.
Varenicline The excretion of Tipiracil can be decreased when combined with Varenicline.
Oxprenolol The excretion of Tipiracil can be decreased when combined with Oxprenolol.
Vandetanib The excretion of Tipiracil can be decreased when combined with Vandetanib.
Histamine The excretion of Tipiracil can be decreased when combined with Histamine.
Pimagedine The excretion of Tipiracil can be decreased when combined with Pimagedine.
Tafenoquine The excretion of Tipiracil can be decreased when combined with Tafenoquine.
Crizotinib The excretion of Tipiracil can be decreased when combined with Crizotinib.
Linagliptin The excretion of Tipiracil can be decreased when combined with Linagliptin.
Dolutegravir The excretion of Tipiracil can be decreased when combined with Dolutegravir.
Lenvatinib The excretion of Tipiracil can be decreased when combined with Lenvatinib.
Dexchlorpheniramine maleate The excretion of Tipiracil can be decreased when combined with Dexchlorpheniramine maleate.
Isavuconazole The excretion of Tipiracil can be decreased when combined with Isavuconazole.
Apalutamide The excretion of Tipiracil can be decreased when combined with Apalutamide.
Erdafitinib The excretion of Tipiracil can be decreased when combined with Erdafitinib.
Enasidenib The excretion of Tipiracil can be decreased when combined with Enasidenib.
Estradiol acetate The excretion of Tipiracil can be decreased when combined with Estradiol acetate.
Estradiol benzoate The excretion of Tipiracil can be decreased when combined with Estradiol benzoate.
Estradiol cypionate The excretion of Tipiracil can be decreased when combined with Estradiol cypionate.
Estradiol dienanthate The excretion of Tipiracil can be decreased when combined with Estradiol dienanthate.
Estradiol valerate The excretion of Tipiracil can be decreased when combined with Estradiol valerate.
Choline salicylate The excretion of Tipiracil can be decreased when combined with Choline salicylate.
Dronedarone The excretion of Tipiracil can be decreased when combined with Dronedarone.
Salmeterol The excretion of Tipiracil can be decreased when combined with Salmeterol.
Tucatinib The excretion of Tipiracil can be decreased when combined with Tucatinib.
Bupropion The excretion of Tipiracil can be decreased when combined with Bupropion.
Methylene blue The excretion of Tipiracil can be decreased when combined with Methylene blue.
Trilaciclib The excretion of Tipiracil can be decreased when combined with Trilaciclib.
Fexinidazole The excretion of Tipiracil can be decreased when combined with Fexinidazole.
Levoketoconazole The excretion of Tipiracil can be decreased when combined with Levoketoconazole.
Dabrafenib The excretion of Tipiracil can be decreased when combined with Dabrafenib.
Capivasertib The excretion of Tipiracil can be decreased when combined with Capivasertib.
Encorafenib The excretion of Tipiracil can be decreased when combined with Encorafenib.
Isavuconazonium The excretion of Tipiracil can be decreased when combined with Isavuconazonium.

Target Protein

Thymidine phosphorylase TYMP

Referensi & Sumber

Artikel (PubMed)
  • PMID: 27162472
    Kish T, Uppal P: Trifluridine/Tipiracil (Lonsurf) for the Treatment of Metastatic Colorectal Cancer. P T. 2016 May;41(5):314-25.
  • PMID: 26428513
    Lenz HJ, Stintzing S, Loupakis F: TAS-102, a novel antitumor agent: a review of the mechanism of action. Cancer Treat Rev. 2015 Nov;41(9):777-83. doi: 10.1016/j.ctrv.2015.06.001. Epub 2015 Jun 6.
  • PMID: 29056855
    Puthiamadathil JM, Weinberg BA: Emerging combination therapies for metastatic colorectal cancer - impact of trifluridine/tipiracil. Cancer Manag Res. 2017 Oct 3;9:461-469. doi: 10.2147/CMAR.S113320. eCollection 2017.
  • PMID: 12639965
    Hotchkiss KA, Ashton AW, Schwartz EL: Thymidine phosphorylase and 2-deoxyribose stimulate human endothelial cell migration by specific activation of the integrins alpha 5 beta 1 and alpha V beta 3. J Biol Chem. 2003 May 23;278(21):19272-9. Epub 2003 Mar 13.
  • PMID: 23182191
    Peters GJ, Bijnsdorp IV: TAS-102: more than an antimetabolite. Lancet Oncol. 2012 Dec;13(12):e518-9. doi: 10.1016/S1470-2045(12)70426-6.
  • PMID: 28111727
    Cleary JM, Rosen LS, Yoshida K, Rasco D, Shapiro GI, Sun W: A phase 1 study of the pharmacokinetics of nucleoside analog trifluridine and thymidine phosphorylase inhibitor tipiracil (components of TAS-102) vs trifluridine alone. Invest New Drugs. 2017 Apr;35(2):189-197. doi: 10.1007/s10637-016-0409-9. Epub 2017 Jan 23.
  • PMID: 26918279
    Yoshino T, Kojima T, Bando H, Yamazaki T, Naito Y, Mukai H, Fuse N, Goto K, Ito Y, Doi T, Ohtsu A: Effect of food on the pharmacokinetics of TAS-102 and its efficacy and safety in patients with advanced solid tumors. Cancer Sci. 2016 May;107(5):659-65. doi: 10.1111/cas.12912. Epub 2016 Mar 28.
  • PMID: 26787503
    Lee JJ, Seraj J, Yoshida K, Mizuguchi H, Strychor S, Fiejdasz J, Faulkner T, Parise RA, Fawcett P, Pollice L, Mason S, Hague J, Croft M, Nugteren J, Tedder C, Sun W, Chu E, Beumer JH: Human mass balance study of TAS-102 using (14)C analyzed by accelerator mass spectrometry. Cancer Chemother Pharmacol. 2016 Mar;77(3):515-26. doi: 10.1007/s00280-016-2965-2. Epub 2016 Jan 19.

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