リファブチン 化学特性,用途語,生産方法
外観
赤色～暗い赤色～褐色粉末～結晶
効能
抗生物質 (抗マイコバクテリア), RNAポリメラーゼ阻害薬
商品名
ミコブティン (ファイザー)
説明
Rifabutin, a rifamycin antibacterial derivative, is the first agent approved and
introduced for the prevention of Mycobacterium avium complex (MAC) in AIDS
patients. It is also indicated in combination chemotherapy for the prophylaxis and
treatment of MAC infections in HIV positive patients and for newly diagnosed and
chronic tuberculosis.
化学的特性
Red-Brown Powder
使用
Rifamycins are antibiotics that inhibit DNA-dependent RNA polymerases and are usually bactericidal against Gram-positive bacteria but bacteriostatic against Gram-negative bacteria. Rifamycins are also effective against Mycobacterium species, including M. tuberculosis. Rifabutin is a broad-spectrum rifamycin antibiotic that has applications against tuberculosis, H. pylori, M. avium complex, Chlamydia, and other bacteria. It is also useful in co-infections with human immunodeficiency virus, including tuberculosis.
適応症
Rifabutin (Mycobutin), an antibiotic related to rifampin,
shares its mechanism of action, that is, inhibition
of RNA polymerase. Rifabutin has significant activity
in vitro and in vivo against M. avium-intracellular
complex (MAC) isolates from both HIV-infected and
non–HIV-infected individuals. It has better activity
against MAC organisms than rifampin. Rifabutin is active
against M. tuberculosis, including some rifampinresistant
strains, such as M.leprae and M.fortuitum. It has
a spectrum of activity against gram-positive and gramnegative
organisms similar to that of rifampin. The molecular
basis for resistance to rifabutin is shared by both
rifampin and rifabutin; this explains the virtually complete
cross-resistance that occurs between these drugs.
抗菌性
The activity is similar to that of rifampicin, but it is more active against the Mycobacterium avium complex (MIC 0.01–2 mg/L) and several other atypical mycobacteria. It inhibits the replication of human immunodeficiency virus 1 (HIV-1) in concentrations (10 mg/L) that are not toxic to lymphoid cells, but no efficacy on HIV infections has been demonstrated.
獲得抵抗性
The frequency of spontaneously resistant mutants in several bacterial species, including M. tuberculosis, M. leprae, Staphylococcus aureus and Chlamydia trachomatis, is somewhat lower than with rifampicin.
応用例（製薬）
Rifabutine; ansamycin. Molecular weight: 847.02.
A semisynthetic spiropiperidyl derivative of rifamycin S, available for oral administration. It is slightly soluble in water and soluble in organic solvents.
薬理学
Rifabutin is well absorbed orally, and peak plasma
concentrations are reached in 2 to 3 hours. Because of
its lipophilicity, rifabutin achieves a 5- to 10-fold higher
concentration in tissues than in plasma. The drug has a
half-life range of 16 to 96 hours and is eliminated in
urine and bile.
Rifabutin appears as effective as rifampin in the
treatment of drug-susceptible tuberculosis and is used
in the treatment of latent tuberculosis infection either
alone or in combination with pyrazinamide. Clinical use
of rifabutin has increased in recent years, especially in
the treatment of HIV infection. It is a less potent
inducer of cytochrome 450 enzymes pathways than rifampin
and results in less drug interaction with the
protease inhibitors and nonnucleoside reverse transcriptase
inhibitors. Rifabutin is therefore commonly
substituted for rifampin in the treatment of tuberculosis
in HIV-infected patients. Another important use of rifabutin
in the HIV-infected population is prevention
and treatment of disseminated MAC.
薬物動態学
Oral absorption：12–20%
C
max 300 mg oral ：0.38 mg/L after 3.3 h
Plasma half-life：16 h
Volume of distribution：9.3 L/kg
Plasma protein binding： 85%
absorption and distribution Oral absorption is rapid but incomplete, with considerable interpatient variation. It is well distributed, concentrations in many organs being higher than that in plasma. The average concentration in lungs is 6.5 times the simultaneous plasma concentration.
Metabolism and excretion Rifabutin is mainly metabolized to the active desacetyl derivative, although several other oxidation products have been detected in urine, where some 10% of the dose is eliminated. About 30–50% of the dose can be recovered from the feces. Elimination from plasma is biphasic, with a terminal half-life of 45 h. The drug is a weak inducer of hepatic enzymes. The rate of metabolism increases, and the plasma area under the concentration–time curve (AUC) declines as the treatment continues.
臨床応用
Prevention of infections with M. avium complex in AIDS patients
Treatment of non-tuberculous mycobacterial disease (in combination with other agents)
Rifabutin in combination with other agents has been proposed as a rescue therapy after Helicobacter pylori treatment failures.Although some efficacy has been observed in the treatment of tuberculosis, its use for this condition is not recommended.
副作用
The adverse effects that most frequently result in
discontinuation of rifabutin include GI intolerance,
rash, and neutropenia. Rifabutin levels will be increased
with concurrent administration of fluconazole and clarithromycin,
resulting in anterior uveitis, polymyalgia
syndrome, and a yellowish-tan discoloration of the skin
(pseudojaundice). Other adverse reactions are similar
to those of rifampin, such as hepatitis, red-orange discoloration
of body fluids, and drug interactions due to
effects on the hepatic P450 cytochrome enzyme system.
リファブチン 上流と下流の製品情報
原材料
準備製品