Identification | |
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Name | Flucytosine |
Accession Number | DB01099 (APRD00299) |
Type | small molecule |
Description | A fluorinated cytosine analog that is used as an antifungal agent. [PubChem] |
Structure |
|
Categories (*) | |
Molecular Weight | 129.0925 |
Groups | approved |
Monoisotopic Weight | 129.03383997 |
Pharmacology | |
Indication | For the treatment (in combination with amphotericin B) of serious infections caused by susceptible strains of Candida (septicemia, endocarditis and urinary system infections) and/or Cryptococcus (meningitis and pulmonary infections). |
Mechanism of action | Although the exact mode of action is unknown, it has been proposed that flucytosine acts directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and indirectly by intracellular metabolism to 5-fluorouracil. Flucytosine enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to 5-fluorouracil within fungal organisms. The 5-fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA and RNA. The result is unbalanced growth and death of the fungal organism. It also appears to be an inhibitor of fungal thymidylate synthase. |
Absorption | Rapidly and virtually completely absorbed following oral administration. Bioavailability 78% to 89%. |
Protein binding | 28-31% |
Biotransformation | Flucytosine is deaminated, possibly by gut bacteria or by the fungal targets, to 5-fluorouracil, the active metabolite. |
Route of elimination | Flucytosine is excreted via the kidneys by means of glomerular filtration without significant tubular reabsorption. A small portion of the dose is excreted in the feces. |
Toxicity | Oral, rat: LD50 = >15 gm/kg. |
Affected organisms |
|
Interactions | |
Drug Interactions | Not Available |
Food Interactions | Not Available |
DNA | |
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Name | DNA |
Gene Name | Not Available |
Pharmacological action | yes |
Actions | cross-linking/alkylation |
References |
|
DTHybrid score | Not Available |
DNA (cytosine-5)-methyltransferase 1 | |
Name | DNA (cytosine-5)-methyltransferase 1 |
Gene Name | DNMT1 |
Pharmacological action | unknown |
Actions | other |
References |
|
DTHybrid score | 1.1316 |
Thymidylate synthase | |
Name | Thymidylate synthase |
Gene Name | TMP1 |
Pharmacological action | unknown |
Actions | inhibitor |
References |
|
DTHybrid score | 1.2102 |
Id | Partner name | Gene Name | Score |
---|---|---|---|
359 | Thymidylate synthase | TYMS | 1.2102 |
2626 | Thymidylate synthase | thyA | 1.2102 |
2729 | Thymidylate synthase | thyA | 1.2102 |
5352 | Thymidylate synthase | THYA | 1.2102 |
3611 | Cytidine deaminase | cdd | 0.1528 |
3707 | Cytidine deaminase | cdd | 0.1528 |
4211 | Cytidine deaminase | CDA | 0.1528 |
4773 | Deoxycytidine kinase | DCK | 0.129 |
6147 | Solute carrier family 22 member 3 | SLC22A3 | 0.0201 |
833 | Organic cation/carnitine transporter 1 | SLC22A4 | 0.02 |
220 | Sodium channel protein type 5 subunit alpha | SCN5A | 0.0199 |
6144 | Solute carrier family 22 member 2 | SLC22A2 | 0.0177 |
118 | Organic cation/carnitine transporter 2 | SLC22A5 | 0.0175 |
3923 | Cholinesterase | BCHE | 0.0171 |
6145 | Solute carrier family 22 member 1 | SLC22A1 | 0.017 |
4119 | Cytochrome P450 2D6 | CYP2D6 | 0.0124 |