クロファジミン 化学特性,用途語,生産方法
外観
黄色～くすんだ黄色～暗い赤色粉末～結晶
効能
ハンセン病治療薬
商品名
ランプレン (サンド)
化学的特性
Red Solid
使用
antiinflammatory, glucocorticoid
定義
ChEBI: 3-Isopropylimino-3,5-dihydro-phenazine in which the hydrogen at position 5 is substituted substituted by a 4-chlorophenyl group, and that at position 2 is substituted by a (4-chlorophenyl)amino group. A dark red crystalline solid, clofazimine is an antimyc
bacterial and is one of the main drugs used for the treatment of multi-bacillary leprosy. However, it can cause red/brown discolouration of the skin, so other treatments are often preferred in light-skinned patients.
適応症
Clofazimine is a weakly bactericidal dye that has some
activity against M. leprae. Its precise mechanism of action
is unknown but may involve mycobacterial DNA
binding. Its oral absorption is quite variable, with 9 to
70% of the drug eliminated in the feces. Clofazimine
achieves significant concentrations in tissues, including
the phagocytic cells; it has a plasma half-life of 70 days.
It is primarily excreted in bile, with less than 1% excretion
in urine.
抗菌性
The mode of action is not fully understood. It has bacteristatic
and weak bactericidal activity against several species of
mycobacteria and some species of Actinomyces and Nocardia.
In-vitro minimum inhibitory concentrations (MICs) are:
M. tuberculosis 0.5 mg/L and M. leprae (assayed in a mouse
model) 0.1–1 mg/L, but these MICs have limited
clinical
relevance as clofazimine shows marked differences in accumulation
in various tissues. Activity against M. leprae is demonstrable
in humans only after 50 days of therapy.
Clofazimine
resistance, although reported, appears to be rare.
応用例（製薬）
One of a number of substituted iminophenazine dyes originally
synthesized as potential antituberculosis agents. It is
almost insoluble in water. It stimulates various phagocyte
functions including release of free oxygen radicals, but it is
not clear whether this contributes to its antimicrobial activity.
It also has anti-inflammatory properties, attributed to its
ability to inhibit certain patterns of intracellular T-cell receptor-
mediated signaling, making it a useful drug for treating
leprosy reactions and possibly other autoimmune processes.
薬物動態学
Clofazimine is well absorbed by the intestine and is taken
up by adipose tissue and cells of the macrophage/monocyte
series, including those in the intestinal wall. It has a very long
half-life (variously estimated as 10–70 days) and is eliminated,
mostly unchanged, in the urine and feces.
薬理学
Clofazimine is a substituted iminophenazine that was first proposed for treating leprosy in
1962; however, it entered into medical practice toward the end of the 1980s. The mechanisms of its action is not definitively known, although there is the assumption that it can
inhibit the formation of matrixes with DNA, which leads to a delay in the growth of
mycobacteria. Clofazimine exhibits a bactericidal effect between that of dapsone and
rifampicin. Synonym of this drug is lamprene.
臨床応用
Multibacillary leprosy (in combination with other anti-leprosy drugs)
Erythema nodosum leprosum (anti-inflammatory activity)
Clofazimine has been suggested as a drug for treatment of
MDR tuberculosis, although its efficacy is unproven. It has
been used to treat M. ulcerans infection (Buruli ulcer) but with
limited responses. Use in disease caused by mycobacteria of
the M. avium complex is no longer recommended as more
effective and less toxic alternative agents are available.
副作用
Clofazimine is usually well tolerated, but some patients develop
nausea, abdominal pain and diarrhea, relieved to some extent
by taking the drug with a meal or glass of milk. Dose-related,
reversible, skin discoloration is very common and is unacceptable
to some patients. Discoloration of the hair, cornea, urine,
sweat and tears also occurs. Infants born to mothers receiving
clofazimine are reversibly pigmented at birth. Edema of the
wall of the small intestine leading to subacute obstruction is
a rare but serious complication of prolonged high-dose therapy
for leprosy reactions. Deposition of clofazimine in lymph
nodes may interfere with lymphatic drainage, occasionally
manifesting as edema of the feet.
純化方法
Clofazimine recrystallises from acetone as dark red crystals. Its solubility in CHCl3 and EtOH is 7% and 0.1%, respectively,at room temperature. It is insoluble in H2O. It is antibacterial. [Barry et al. J Chem Soc 859 1958, Beilstein 25 III/IV 3033.]
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原材料
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