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外観
赤黄色〜黄赤色, 結晶性粉末〜粉末
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溶解性
エタノール及びアセトンに溶け、水にほとんど溶けない。
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用途
高速液体クロマトグラフ法によるリファキシミン定量用標準品。
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効能
抗生物質, 高アンモニア血症治療薬
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商品名
リフキシマ (あすか製薬)
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説明
Rifaximin is an antibiotic structurally related to rifamycin. It is reported to be efficacious
in the treatment of gastrointestinal infections and hepatic encephalopathy, being highly
active against Gram-positive and -negative aerobic and anaerobic bacteria. Due to poor
systemic absorption, rifaximin is effective in presurgical sterilization of the GI tract.It displays good activity against a wide spectrum of bacteria,
including Salmonella spp., S. aureus, and E. coli.
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化学的特性
Red-Orange Crystalline Powder
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使用
Rifaximin is a non-absorbable semisynthetic Rifamycin antibiotic.
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定義
ChEBI: A semisynthetic member of the class of rifamycins and non-systemic gastrointestinal site-specific broad spectrum antibiotic. Used in the treatment of traveller's diarrhoea, hepatic encephalopathy and irritable bowel syndrome.
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抗菌性
The in-vitro activity is slightly inferior to that of rifampicin. The MIC90 for Gram-positive cocci is well below 1 mg/L, with the exception of enterococci (MIC 2–8 mg/L). Among intestinal pathogens C. difficile is sensitive (MIC90 0.8 mg/L), Esch. coli, Salmonella spp. and Shigella spp. are inhibited by 4–8 mg/L. Campylobacter jejuni is mostly insensitive.
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応用例（製薬）
A semisynthetic derivative of rifamycin S formulated for oral administration. It is poorly absorbed from the gastrointestinal tract, where its high concentrations are effective against a variety of gastrointestinal pathogens.
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作用機序
The mechanism of action of pyrazinamide is unknown, but recent findings suggest that pyrazinamide may be active either totally or in part as a pro-drug. Susceptible organisms produce pyrazinamidase, which is responsible for conversion of pyrazinamide to pyrazinoic acid intracellularly. Mutation in the pyrazinamidase gene (pncA) results in resistant strains of M . tuberculosis. Pyrazinoic acid has been shown to possess biological activity at a pH 5.4 or lower, in contract in vitro tests that show pyrazinoic acid is 8- to 16-fold less active than pyrazinamide . Pyrazinoic acid may lower the pH in the immediate surroundings of the M . tuberculosis to such an extent that the organism is unable to grow, but this physicochemical property appears to account for only some of the activity. The protonated pyrazinoic acid also can permeate the mycobacterial membrane to lower the pH of the cytoplasm. Recent evidence suggests that pyrazinoic acid decreases membrane potential in older, nonreplicating bacilli, thus decreasing membrane transport, and interferes with the energetics of the membrane.
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薬物動態学
Oral absorption is very low. However, a fraction of the dose may be absorbed and rapidly eliminated through the bile. A 400 mg oral dose produces a maximum plasma concentration of 3.8 mg/L after 1.2 h. The plasma half-life is 5.8 h. Up to 90% of the administered dose is concentrated in the gut, less than 0.2% in the liver and kidney, and less than 0.01% in other tissues.
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臨床応用
It is used for a variety of gastrointestinal diseases, including the treatment of traveler’s diarrhea. Preliminary results
suggest clinical efficacy in the therapy of hepatic encephalopathy and of C. difficile infections.
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副作用
Oral doses up to 100 mg/kg for 6 months produced no significant signs of toxicity to rats. Teratogenic effects in rats and rabbits have been reported (pregnancy category C).
Very few adverse effects were reported during human treatment, mostly gastrointestinal discomfort. Prolonged therapy was associated with infrequent urticarial skin reactions.
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代謝
Pyrazinamide is readily absorbed after oral administration, but little of the intact molecule is excreted unchanged. The major metabolic route consists of hydrolysis by hepatic microsomal pyrazinamidase to pyrazinoic acid, which may then be oxidized by xanthine oxidase to 5-hydroxypyrazinoic acid. The latter compound may appear in the urine either free or as a conjugate with glycine.
