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外観
白色～うすい黄色粉末～結晶
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効能
抗真菌薬, エルゴステロール合成阻害薬
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説明
Posaconazole, launched in the UK, is the newest member of the azole
class of antifungal agents to reach the market. It is indicated for the treatment and
prophylaxis of a range of invasive fungal infections, including aspergillosis,fusariosis, chromoblastomycosis, mycetoma, and coccidiomycosis in patients
who are refractory to, or intolerant of, standard therapy with amphotericin B
and/or itraconazole. In the US, it is approved for the prophylaxis of invasive
Aspergillus and Candida infections in patients 13 years of age who are at high
risk of developing these infections due to being severely immunocompromised.
Additionally, it is approved for the treatment of oropharyngeal candidiasis.
Posaconazole has an expanded spectrum of activity over other members of the
azole antifungals. In addition to potent activity against refractory cases of
aspergillosis and fluconazole-resistant Candida, it demonstrates activity against
Zygomycetes.
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化学的特性
White Solid
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使用
Posaconazole is a sterol C14ɑ demethylase inhibitor with an IC50 of 0.25 nM
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定義
ChEBI: An N-arylpiperazine that consists of piperazine carrying two 4-substituted phenyl groups at positions 1 and 4. A triazole antifungal drug.
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抗菌性
The spectrum includes dimorphic fungi (Blast. dermatitidis,
Coccidioides spp., Hist. capsulatum, Pen. marneffei, and Spor.
schenckii), molds (Aspergillus spp., Mucor spp., Rhizomucor
spp. and Rhizopus spp.), some dematiaceous fungi and yeasts
(Candida spp. and Cryptococcus spp.).
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一般的な説明
Technetium (99mTc) exametazime is a mixture of unstablelipophilic enantiomers that rapidly cross the blood-brain barrierand is trapped in the tissues. The proposed trapping mechanismfor localization includes reduction by glutathione. Asimilar diffusion and trapping process occurs with autologouslymphocytes in vitro.
Exametazime is also known as hexamethylpropyleneamineoxime or HMPAO. The radiolabeled complex is indicated for cerebral perfusion in stroke, but is most commonlyused for the radiolabeling of autologous leukocytesas an adjunct in the localization of intra-abdominal infectionand inflammatory bowel disease.
Each kit includes several components: (a) reaction vialscontaining a mixture of exametazime, stannous chloride,and sodium chloride; (b) vials of 1% methylene blue; (c)vials of phosphate buffer in 0.9% NaCl; and (d) 0.45-μm syringefilters. Product preparation depends on the intendeduse.
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応用例（製薬）
A synthetic triazole available for oral administration.
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薬物動態学
Cmax 200 mg oral: 0.5 mg/L after 4 h
Plasma half-life: 35 h
Volume of distribution: 1774 L
Plasma protein binding: >98%
Absorption
Oral absorption is slow. Absorption from the gastrointestinal tract is improved if the drug is given with a high-fat meal. Blood concentrations increase in proportion to dosage up to 800 mg.
Distribution
It is extensively distributed into body tissues.
Metabolism and excretion
It is not as extensively metabolized by the hepatic cytochrome P450 system as other triazole antifungals. More than 70% of an administered dose is eliminated in the feces, predominantly as unchanged drug. The remainder is excreted as glucuronidated derivatives in the urine. Posaconazole is a substrate for intestinal P-glycoprotein,an adenosine triphosphate-dependent plasma membrane transporter responsible for drug efflux from cells. Multiple peaks in blood concentrations have been observed, suggesting that effluxed drug is reabsorbed into the systemic circulation.
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臨床応用
Invasive aspergillosis
Fusarium infection
Chromoblastomycosis and mycetoma
Coccidioidomycosis
Oropharyngeal candidosis
Prophylaxis of invasive fungal infections in patients at serious risk
With the exception of oropharyngeal candidosis and prophylaxis,
use is presently restricted to patients with disease that
is refractory to other antifungal drugs, or who are intolerant
to them.
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副作用
It is generally well tolerated even for long periods. Unwanted
effects include gastrointestinal discomfort and mild to moderate,
transient abnormalities of liver enzymes. Rare side effects
include cholestasis and hepatic failure.
