플루시토신

플루시토신 속성

플루시토신 MSDS

2-Hydroxy-4-amino-5-fluoropyrimidine

플루시토신 C화학적 특성, 용도, 생산

개요

5-Fluorocytosine (5-FC), a fluorinated pyrimidine analog, is a synthetic antimycotic prodrug that is converted by cytosine deaminase to 5-fluorouracil. 5-Fluorouracil, a widely used cytotoxic drug, is further metabolized to fluorinated ribo- and deoxyribonucleotides, resulting in the inhibition of DNA and protein synthesis, which has multiple effects including inhibition of Candida species and C. neoformans infections and cytotoxicity towards cancer cells. In combination with a retroviral replicating vector carrying a cytosine deaminase prodrug-activating gene, 5-FC has been shown to selectively eliminate CT26 and Tu-2449 tumor cells in vitro (IC₅₀s = 4.2 and 1.5 μM, respectively) and to significantly improve survival and reduce tumor size (at a dose of 500 mg/kg) in two different syngeneic mouse glioma models.

화학적 성질

White Crystalline Solid

용도

5-Fluorocytosine acts as an antidiabetic, antifungal and antimicrobial agent. It is useful for the treatment of serious infections arises due to susceptible strains of Candida or Cryptococcus neoformans and chromomycosis. Further, it is employed in studies on TMP biosynthesis.

Indications

Flucytosine (Ancobon) is a synthetic, fluorinated pyrimidine that is structurally related to fluorouracil (FU) and floxuridine. It can be fungistatic and fungicidal. Although it is used more frequently in the treatment of systemic infections caused by Candida and Cryptococcus, dermatologic indications may include infections due to chromomycosis, sporotrichosis, Cladosporium, and Sporothrix species. It is generally ineffective against Aspergillus species.

정의

ChEBI: Flucytosine is an organofluorine compound that is cytosine that is substituted at position 5 by a fluorine. A prodrug for the antifungal 5-fluorouracil, it is used for the treatment of systemic fungal infections. It has a role as a prodrug. It is an organofluorine compound, a pyrimidone, an aminopyrimidine, a nucleoside analogue and a pyrimidine antifungal drug. It is functionally related to a cytosine.

Antimicrobial activity

The spectrum of activity is restricted to Candida spp., Cryptococcus spp. and some fungi causing chromoblastomycosis.

원료

About 2–3 of Candida spp. isolates (more in some centers) are resistant before treatment starts, and resistance may develop during treatment. The most common cause of resistance appears to be loss of the enzyme uridine monophosphate pyrophosphorylase.

Pharmaceutical Applications

A synthetic fluorinated pyrimidine available for intravenous infusion or oral administration.

Mechanism of action

Flucytosine (5-flucytosine, 5-FC; Ancoban) is a fluorinated pyrimidine analogue of cytosine that was originally synthesized for possible use as an antineoplastic agent. It is indicated only for the treatment of serious systemic infections caused by susceptible strains of Candida and Cryptococcus spp.The mechanism of action of 5-fluorocytosine (5-FC)has been studied in detail.The drug enters the fungal cell by active transport onATPases that normally transport pyrimidines. Once insidethe cell, 5-fluorocytosine is deaminated in a reaction catalyzedby cytosine deaminase to yield 5-fluorouracil(5-FU). 5-Fluorouracil is the active metabolite of the drug.5-Fluorouracil enters into pathways of both ribonucleotideand deoxyribonucleotide synthesis. The fluororibonucleotidetriphosphates are incorporated into RNA, causingfaulty RNA synthesis. This pathway causes cell death. Inthe deoxyribonucleotide series, 5-fluorodeoxyuridinemonophosphate (F-dUMP) binds to 5,10-methylenetetrahydrofolicacid, interrupting the one-carbon pool substratethat feeds thymidylate synthesis. Hence, DNA synthesisis blocked.

Pharmacology

5-FC is well absorbed orally, with greater than 90% bioavailability. The serum half-life is 3 to 5 hours, with serum levels peaking 4 to 6 hours after a single dose.The drug is widely distributed in body fluids, with cerebrospinal fluid levels 60 to 80% of serum levels.The drug also penetrates well into urine, aqueous humor, and bronchial secretions.Minimal serum protein binding allows more than 90% of each dose to be excreted in the urine; significant dosage reductions are required in the presence of renal impairment. 5-FC can be removed by both hemodialysis and peritoneal dialysis. 5-FC conversion to toxic metabolites may occur in mammalian cells to a limited extent, which accounts for 5-FC toxicity.

Pharmacokinetics

Oral absorption: Complete
C_max 25 mg/kg 6-hourly oral: 70–80 mg/L after 1–2 h
Plasma half-life: 3–6 h
Volume of distribution: 0.7–1 L/kg
Plasma protein binding c. 12%
Absorption is slower in persons with impaired renal function, but peak concentrations are higher. Levels in the CSF are around 75% of the simultaneous serum concentration. More than 90% of a dose of flucytosine is excreted in the urine in unchanged form. The serum half-life is much longer in renal failure, necessitating modification of the dosage regimen: for patients with a creatinine clearance below 40 mL/ min the dosage interval should be doubled to 12 h; in severe renal failure the dosage interval should be further increased to once daily or less, based on frequent serum drug concentration measurements.

부작용

Nausea, vomiting, abdominal pain and diarrhea are common. Serious side effects include myelosuppression and hepatic toxicity; they occur more frequently when serum concentrations exceed 100 mg/L.
The nephrotoxic effects of amphotericin B can result in elevated blood concentrations of flucytosine, and levels of the latter drug should be monitored when these compounds are administered together. When 5-FC is prescribed alone to patients with normal renal function, skin rash, epigastric distress, diarrhea, and liver enzyme elevations can occur.

신진 대사

Flucytosine itself is not cytotoxic but, rather, is a pro-drug that is taken up by fungi and metabolized to 5-fluorouracil (5-FU) by fungal cytidine deaminase. Then, 5-FU is converted to 5-fluorodeoxyuridine, which as a thymidylate synthase inhibitor interferes with both protein and RNA biosynthesis. 5-Fluorouracil is cytotoxic and is employed in cancer chemotherapy. Human cells do not contain cytosine deaminase and, therefore, do not convert flucytosine to 5-FU. Some intestinal flora, however, do convert the drug to 5-FU, so human toxicity does result from this metabolism.

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플루시토신 공급 업체

공급자	전화	이메일	국가	제품 수	이점
Anhui Royal Chemical Co., Ltd.	+86-25-86655873 +8613962173137	marketing@royal-chem.com	China	192	55
Ningxia Jinhua Chemical Co.,Ltd	025-52279164	info@nxjhchem.com	China	79	58
Hangzhou Measure Life Technology Co., LTD	+8613343730176	2924244016@qq.com	China	83	58
Guangzhou Tosun Pharmaceutical Limited	+8618922120635	sales@toref-standards.com	China	998	58
Xinxiang Aurora Biotechnology Co.,Ltd.	+86-0086-0373-3088722 +8618637352520	info@aurora-biotech.com	China	89	58
Hebei Chuanghai Biotechnology Co,.LTD	+86-13131129325	sales1@chuanghaibio.com	China	5893	58
Henan Bao Enluo International TradeCo.，LTD	+86-17331933971 +86-17331933971	deasea125996@gmail.com	China	2472	58
Shaanxi Haibo Biotechnology Co., Ltd	+undefined18602966907	qinhe02@xaltbio.com	China	997	58
Henan Fengda Chemical Co., Ltd	+86-371-86557731 +86-13613820652	info@fdachem.com	China	20288	58
hebei hongtan Biotechnology Co., Ltd	+86-86-1913198-3935 +8617331935328	sales03@chemcn.cn	China	970	58

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