ボリコナゾール 化学特性,用途語,生産方法
外観
白色～ほとんど白色粉末～結晶
用途
カンジダ菌に対し強力な作用を示します。トリアゾール系抗真菌薬作用を示します。
用途
カンジダ属に対し強力な作用を示します。トリアゾール系抗真菌薬作用を示します。
効能
抗真菌薬, エルゴステロール合成阻害薬
商品名
ブイフェンド (ファイザー); ブイフェンド (ファイザー); ブイフェンド (ファイザー)
説明
Voriconazole is a broad-spectrum triazole antifungal ,it is primarily used for the treatment of progressive, possibly life-threatening infections in immune deficiency patients. Indications include: immunosuppressed patients with severe fungal infections, acute invasive aspergillosis (the most common pathogen is Aspergillus fumigatus, followed by A. flavus, Aspergillus niger and Aspergillus soil), severe invasive infections caused by fluconazole-resistant Candida (including C. krusei) severe infection caused by Foot actinomycetes bacteria genus and Fusarium bacteria genus . Moderate to severe renal insufficiency is administered intravenously paying caution.
化学的特性
Cyrstalline Solid
使用
Voriconazole is an antifungal (systemic) that belong to an ergosterol biosynthesis inhibitor. It is used to treat serious fungal or yeast infections, such as aspergillosis (fungal infection in the lungs), candidemia (fungal infection in the blood), esophageal candidiasis (candida esophagitis), or other fungal infections (infections in the skin, stomach, kidney, bladder, or wounds).
適応症
Voriconazole (Vfend), a derivative of fluconazole, is a
second-generation triazole that has improved antifungal
activity against Aspergillus and Fusarium spp., P.
boydii, Penicillium marneffei, and fluconazole-resistant
Candida spp. Like fluconazole, voriconazole has high
oral bioavailability and good cerebrospinal fluid penetration,
but unlike fluconazole, it undergoes extensive
hepatic metabolism and is highly protein bound. No significant
amount of bioactive drug is excreted into the
urine. Dosage reduction is necessary with severe hepatic
insufficiency but not with renal insufficiency.
定義
ChEBI: Voriconazole is a triazole-based antifungal agent used for the treatment of esophageal candidiasis, invasive pulmonary aspergillosis, and serious fungal infections caused by Scedosporium apiospermum and Fusarium spp. It is an inhibitor of cytochrome P450 2C9 (CYP2C9) and CYP3A4. It has a role as a P450 inhibitor. It is a member of pyrimidines, a difluorobenzene, a tertiary alcohol, a triazole antifungal drug and a conazole antifungal drug.
抗菌性
The spectrum includes most fungi that cause human disease:
dimorphic fungi (Blast. dermatitidis, Coccidioides spp., Hist. capsulatum,
Paracocc. brasiliensis, Pen. marneffei and Spor. schenckii),
molds (Aspergillus spp., Fusarium spp. and Scedosporium spp.),
dematiaceous fungi and yeasts (Candida spp., Cryptococcus
spp. and Trichosporon spp.).
獲得抵抗性
Some fluconazole- and itraconazole-resistant strains of
Candida and Aspergillus spp. show reduced susceptibility to
voriconazole.
一般的な説明
Voriconazole is a synthetically prepared, broad-spectrum triazole derivative of fluconazole, which shows
in vitro activity against many yeasts and a broad-spectrum of mold and dermatophyte isolates. Its mode of action involves the inhibition of cytochrome P450 (CYP)-dependent enzyme, 14-α-sterol demethylase, and hence it is involved in disrupting the cell membrane and terminate the fungal growth.
応用例（製薬）
Voriconazole is a triazole, antifungal agent that inhibits a broad range of pathogenic yeasts, including Candida (MIC = 0.03-8 μg/ml), and filamentous fungi such as Aspergillus, Scedosporium, and Fusarium. Its inhibitory action results from its ability to inhibit the synthesis of ergosterol, the major sterol of the fungal cell membrane.
生物活性
Voriconazole is an triazole antifungal agent used to treat serious fungal infections. It inhibits ergosterol synthesis by inhibiting CYP450-dependent 14-α sterol demethylase resulting in a depletion of ergosterol in fungal cell membranes. Displays potent activity against Candida , Cryptococcus and Aspergillus species.
薬物動態学
Oral absorption: 96%
C
max 400 mg oral: c. 2 mg/L after 2 h
Plasma half-life: c. 6 h
Volume of distribution: 4.6 L/kg
Plasma protein binding: 58%
Absorption
Oral absorption is rapid and almost complete, and is unaffected by intragastric pH. In adults, there is a disproportionate increase in blood concentrations with increasing oral and parenteral dosage, due to partial saturation of first-pass metabolism. In children given low dosages of the drug, proportional changes in drug levels are seen.
Distribution
It is widely distributed into body tissues and fluids, including brain and CSF.
Metabolism and excretion
It is extensively metabolized by the liver. More than 80% of a dose appears in the urine, but less than 2% is excreted in unchanged form. It is metabolized by several different hepatic cytochrome P
450 enzymes. Some people with point mutations in the genes encoding these enzymes are poor metabolizers while others are extensive metabolizers. Drug levels are as much as four-fold lower in individuals who metabolize the drug more extensively.
臨床応用
Acute and chronic invasive aspergillosis
Serious invasive Candida infections
Serious infections caused by Scedosporium and Fusarium spp.
副作用
Unwanted effects include mild to moderate visual disturbance,
rashes, and transient abnormalities of liver enzymes.
Rare side effects include life-threatening hepatitis.
Mode of action
Voriconazole is structurally related to fluconazole (Pfizer, diflucan) and acts by inhibiting the cytochrome P450- dependant enzyme 14a-sterol demethylase of ergosterol synthesis (thereby resulting in the formation of a cell membrane with abnormal characteristics and accumulation of toxic sterol intermediates). Voriconazole was more active than itraconazole and fluconazole against Cryptococcus neoformans and a variety of Candidas species such as C. albicans, C. glabrata C. krusei. It also exhibits similar or superior activity compared to amphotericin B and itraconazole against filamentous fungi such as Aspergillus, an important pathogen which is not susceptible to fluconazole.
予防処置
Significant drug interactions include cyclosporins(increased cyclosporine levels), phenytoin, rifampin,and rifabutin (decreased voriconazole levels). Becauseof its low toxicity profile, this drug may gain importancein the chronic treatment of infections with invasive dimorphicfungi and resistant Candida spp.
ボリコナゾール 上流と下流の製品情報
原材料
水素
水酸化パラジウム / 炭素
Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S,4R)-, compd. with (αR,βS)-α-(2,4-difluorophenyl)-5-fluoro-β-methyl-α-(1H-1,2,4-triazol-1-ylmethyl)-4-pyrimidineethanol (1:1)
Pyrimidine, 4-ethenyl-5-fluoro-
1-(2,4-ジフルオロフェニル)-2-(1H-1,2,4-トリアゾール-1-イル)エタン-1-オン
Voriconazole Impurity 19
3-(6-クロロ-5-フルオロピリミジン-4-イル)-2-(2,4-ジフルオロフェニル)-1-(1H-1,2,4-トリアゾール-1-イル)ブタン-2-オール塩酸塩
(2R,3S/2S,3R)-3-(4-Chloro-5-fluoro-6-pyrimidinyl)-2-(2,4-difluorophenyl)butan-2-ol hydrochloride
(-)-10-カンファースルホン酸
準備製品