Details of the Drug

General Information of Drug (ID: DM13VTW)

• Drug Name: Flucytosine
• Synonyms: Alcobon; Ancobon; Ancotil; Ancotyl; Flucitosina; Flucystine; Flucytosin; Flucytosinum; Flucytosone; Fluocytosine; Fluorcytosine; Fluorocytosine; Flucitosina [DCIT]; F0321; LT00771985; Ancobon (TN); Flucytosinum [INN-Latin]; GL663142 & 5FC; Ro 2-9915; Ro 29915 E/265601; Ro-2-9915; Flucytosine (JP15/USP/INN); Flucytosine [USAN:INN:BAN:JAN]; Cytosine, 5-fluoro-(6CI,7CI,8CI); GL663142 & 4-Amino-5-fluoropyrimidin-2(1H)-one; 2(1H)-Pyrimidinone, 4-amino-5-fluoro-); 2-Hydroxy-4-amino-5-fluoropyrimidine; 4-Amino-5-fluoro-2(1H)-pyrimidinone; 4-Amino-5-fluoro-2-hydroxypyrimidine; 4-Amino-5-fluoro-2-hyroxypyrimidine; 4-Amino-5-fluoropyrimidin-2(1H)-one; 5-FC; 5-Flucytosine; 5-Fluorocystosine; 5-Fluorocytosin; 5-Fluorocytosine; 5-Fluorocytosine-6-3H; 5-Flurocytosine; 5-fluoro cytosine; 5987P; 6-Amino-2-oxo-5-fluoropyrimidine; 6-amino-5-fluoro-1H-pyrimidin-2-one; 9074P

Indication

Disease Entry	ICD 11	Status	REF
Endocarditis	BB40-BA42	Approved	[1], [2]

• Therapeutic Class: Antifungal Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 129.09
  Topological Polar Surface Area (xlogp); -0.9
  Rotatable Bond Count (rotbonds); 0
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
  Bioavailability: 84% of drug becomes completely available to its intended biological destination(s) [4]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 2 mL/min/kg [5]
  Elimination: 99% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 2.4 - 4.8 hours [5]
  Metabolism: The drug is metabolized via the gut bacteria or by the fungal targets to 5-fluorouracil (the active metabolite) [6]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1161.94055 micromolar/kg/day [7]
  Unbound Fraction: The unbound fraction of drug in plasma is 1% [5]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.68 L/kg [5]
  Water Solubility: The ability of drug to dissolve in water is measured as 15 mg/mL [3]
• Chemical Identifiers:
  Formula: C4H4FN3O
  IUPAC Name: 6-amino-5-fluoro-1H-pyrimidin-2-one
  Canonical SMILES: C1=NC(=O)NC(=C1F)N
  InChI: InChI=1S/C4H4FN3O/c5-2-1-7-4(9)8-3(2)6/h1H,(H3,6,7,8,9)
  InChIKey: XRECTZIEBJDKEO-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 3366
  ChEBI ID: CHEBI:5100
  CAS Number: 2022-85-7
  DrugBank ID: DB01099
  TTD ID: D0S5WG
  INTEDE ID: DR2287
  ACDINA ID: D00281

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Candida Thymidylate synthase (Candi TMP1)	TTU6BFZ	TYSY_CANAL	Inhibitor	[1]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Flucytosine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Flucytosine and Ocrelizumab.	Multiple sclerosis [8A40]	[18]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive myelosuppressive effects by the combination of Flucytosine and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[19]
Valganciclovir	DMS2IUH	Moderate	Increased risk of nephrotoxicity by the combination of Flucytosine and Valganciclovir.	Virus infection [1A24-1D9Z]	[20]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Allura red AC dye	E00338	33258	Colorant
Butylparaben	E00142	7184	Antimicrobial preservative
FD&C blue no. 1	E00263	19700	Colorant
methylparaben	E00149	7456	Antimicrobial preservative
Propyl 4-hydroxybenzoate	E00141	7175	Antimicrobial preservative
Quinoline yellow WS	E00309	24671	Colorant
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Sunset yellow FCF	E00255	17730	Colorant
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Potassium hydroxide	E00233	14797	Alkalizing agent
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Sodium hydroxide	E00234	14798	Alkalizing agent
Sodium propionate	E00445	2723816	Antimicrobial preservative
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Water	E00035	962	Solvent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Flucytosine 250 mg capsule	250 mg	Oral Capsule	Oral
Flucytosine 500 mg capsule	500 mg	Oral Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Antifungal agents: mode of action in yeast cells. Rev Esp Quimioter. 2006 Jun;19(2):130-9.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] BDDCS applied to over 900 drugs
• [4] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [5] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [6] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [7] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [8] The efficacy of the combination therapy of 5-fluorouracil, cisplatin and leucovorin for hepatocellular carcinoma and its predictable factors. Cancer Chemother Pharmacol. 2004 Apr;53(4):296-304.
• [9] Loss of folylpoly-gamma-glutamate synthetase activity is a dominant mechanism of resistance to polyglutamylation-dependent novel antifolates in multiple human leukemia sublines. Int J Cancer. 2003 Feb 20;103(5):587-99.
• [10] Updated clinical information on multitargeted antifolates in lung cancer. Clin Lung Cancer. 2009 Mar;10 Suppl 1:S35-40.
• [11] Trifluorothymidine induces cell death independently of p53. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):699-703.
• [12] UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res. 2005 Feb 1;11(3):1226-36.
• [13] DNA damage and homologous recombination signaling induced by thymidylate deprivation. Biochem Pharmacol. 2008 Oct 15;76(8):987-96.
• [14] Antisense down-regulation of thymidylate synthase to suppress growth and enhance cytotoxicity of 5-FUdR, 5-FU and Tomudex in HeLa cells. Br J Pharmacol. 1999 Aug;127(8):1777-86.
• [15] Decreased levels of UMP kinase as a mechanism of fluoropyrimidine resistance. Mol Cancer Ther. 2009 May;8(5):1037-44.
• [16] A phase I study of the lipophilic thymidylate synthase inhibitor Thymitaq (nolatrexed dihydrochloride) given by 10-day oral administration. Br J Cancer. 1999 Feb;79(5-6):915-20.
• [17] Cooperative inhibition of human thymidylate synthase by mixtures of active site binding and allosteric inhibitors. Biochemistry. 2007 Mar 13;46(10):2823-30.
• [18] Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
• [19] Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
• [20] Cerner Multum, Inc. "Australian Product Information.".