Chemical formula: C₂₇H₂₂Cl₂N₄ Molecular mass: 473.396 g/mol PubChem compound: 2794
Clofazimine is an antimycobacterial drug.
Clofazimine exerts a slow bactericidal effect on Mycobacterium leprae (Hansen’s bacillus). Clofazimine inhibits mycobacterial growth and binds preferentially to mycobacterial DNA. Clofazimine also exerts anti-inflammatory properties in treating erythema nodosum leprosum reactions. However, its precise mechanisms of action are unknown.
The mechanism of action for the antimycobacterial activity of clofazimine can be postulated through its membranedirected activity including the bacterial respiratory chain and ion transporters. Intracellular redox cycling, involving oxidation of reduced clofazimine, leads to the generation of antimicrobial reactive oxygen species (ROS), superoxidehydrogen peroxide (H2O2). Secondly, interaction of clofazimine with membrane phospholipids results in the generation of antimicrobial lysophospholipids, which promote membrane dysfunction, resulting in interference with K+ uptake. Both mechanisms result in interference with cellular energy metabolism by disrupting ATP production. Anti-inflammatory activity of clofazimine is primarily through inhibition of T lymphocyte activation and proliferation. Clofazimine may indirectly interfere with the proliferation of T cells by promoting the release of ROS and E-series prostaglandins (PGs), especially PGE2 from neutrophils and monocytes.
Measurement of the minimum inhibitory concentration (MIC) of clofazimine against leprosy bacilli in vitro is not yet feasible.
Clofazimine does not show cross-resistance with dapsone or rifampin.
Clofazimine has a variable absorption rate in leprosy patients, ranging from 45% to 62% after oral administration of clofazimine. The average serum concentrations of clofazimine in leprosy patients treated with clofazimine 100 mg and 300 mg daily were 0.7 mcg/mL and 1 mcg/mL, respectively.
Time to reach peak plasma concentration (median Tmax) of clofazimine decreases from 12 hours to 8 hours under fed conditions relative to the fasted state.
Clofazimine is highly lipophilic and tends to be deposited predominantly in fatty tissue and in cells of the reticuloendothelial system. It is taken up by macrophages throughout the body. In autopsies performed on leprosy patients who had received clofazimine, clofazimine crystals were found predominantly in the mesenteric lymph nodes, adrenals, subcutaneous fat, liver, bile, gall bladder, spleen, small intestine, muscles, bones, and skin.
Clofazimine is bound to alpha- and beta-lipoproteins in serum, particularly the beta-lipoproteins, and the binding was saturable at plasma concentrations of approximately 10 mcg/mL. Binding to gamma-globulin and albumin was negligible.
Three clofazimine metabolites were found in urine following repeated oral doses of clofazimine. Information on the metabolism of clofazimine is limited.
After ingestion of a single 300 mg dose of clofazimine, elimination of unchanged clofazimine and its metabolites in a 24-hour urine collection was negligible. Part of the ingested drug recovered from the feces may represent excretion via the bile. A small amount is also eliminated in the sputum, sebum, and sweat. The elimination half-life of clofazimine following repeated oral doses of 50 or 100 mg clofazimine in leprosy patients was highly variable with estimates ranging from 6.5 to 160 days. The overall mean half-life of clofazimine in these leprosy patients was approximately 25 days.
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