Disease relevance of Lamprene

• CONCLUSIONS: In patients with AIDS and M. avium complex bacteremia, treatment with the three-drug regimen of rifabutin, ethambutol, and clarithromycin leads to resolution of the bacteremia more frequently and more rapidly than treatment with rifampin, ethambutol, clofazimine, and ciprofloxacin, and survival rates are better [1].
• Treatment of chronic graft-versus-host disease with clofazimine [2].
• Thus, clofazimine is safe and has encouraging efficacy in cGVHD, particularly if sclerodermatous skin, joint contractures, or oral manifestations are present [2].
• Clofazimine, a riminophenazine antimicrobial agent, and its analogue B669 were investigated for their effects on FaDu cells, a human squamous carcinoma cell line [3].
• Kussmaul respiration and abdominal pain secondary to metabolic acidosis in AIDS patients with disseminated Mycobacterium avium complex infection receiving clofazimine [4].

High impact information on Lamprene

• Bull's eye retinopathy and clofazimine [5].
• Methemoglobinemia secondary to clofazimine treatment for chronic graft-versus-host disease [6].
• The mechanism by which clofazimine induces a response is unknown, but might be secondary to suppression of alloreactive T-cell function in cGVHD target organs [2].
• The riminophenazine agents clofazimine and B669 inhibit the proliferation of cancer cell lines in vitro by phospholipase A2-mediated oxidative and nonoxidative mechanisms [3].
• These observations demonstrate that the tumoricidal properties of clofazimine and B669 are probably due to increases in the lysophospholipid content of cell membranes [3].

Chemical compound and disease context of Lamprene

• CONCLUSIONS: A rapid reduction in symptoms and bacteremia can be achieved as early as week 2 of therapy using an oral regimen of rifampin, ethambutol, clofazimine, and ciprofloxacin [7].
• Twenty-four patients with newly diagnosed lepromatous leprosy were allocated randomly to three groups and treated for 56 days with 400 mg of ofloxacin daily, 800 mg of ofloxacin daily, or 400 mg of ofloxacin, 100 mg of dapsone, and 50 mg of clofazimine daily plus 300 mg of clofazimine once every 28 days [8].
• Sixty human immunodeficiency virus 1-infected patients who had at least one blood culture positive for M. avium complex were randomized to receive either clofazimine (200 mg), ethambutol (15 mg/kg), or rifampin (600 mg) once daily for 4 weeks [9].
• In vivo activity of amikacin alone or in combination with clofazimine or rifabutin or both against acute experimental Mycobacterium avium complex infections in beige mice [10].
• The mycobacterial response was evaluated for patients with Mycobacterium avium-intracellulare complex (MAC) bacteremia treated with a quadruple regimen of rifabutin, clofazimine, isoniazid, and ethambutol [11].

Biological context of Lamprene

• Clinical pharmacokinetics of clofazimine. A review [12].
• At concentrations of 5 X 10(-6) M to 5 X 10(-3) M clofazimine caused a progressive dose-dependent inhibition of neutrophil motility without detectable effects on phagocytosis, postphagocytic hexose-monophosphate shunt activity, or myeloperoxidase-mediated iodination [13].
• These results suggest that selective inhibition of tumour energy metabolism with agents such as Clofazimine is a potential novel approach to cancer treatment [14].
• We have studied the bioavailability of clofazimine following administration of a single dose of the drug in the biodegradable polymer polylactic-co-glycolic acid (PLGA) [15].
• Skin biopsy samples were obtained from patients before and after 3 months of clofazimine therapy, and the expression of cell adhesion and activation molecules was assessed by an immunohistochemical technique [16].

Anatomical context of Lamprene

• Pretreatment bloodstream MAC isolates from 38 patients with AIDS, previously treated in a randomized fashion with either ethambutol, rifampin, or clofazimine, were tested by three conventional methods using broth or agar, as well as by cocultivation with macrophages [17].
• An in vitro comparison of the effects of the prooxidative riminophenazines clofazimine and B669 on neutrophil phospholipase A2 activity and superoxide generation [18].
• These observations demonstrate that LPC, and to a lesser extent AA, generated during exposure of human neutrophils to clofazimine or B669 are the primary mediators of the prooxidative interactions of these riminophenazines with phagocytes [18].
• Over the same concentration range, clofazimine inhibited lymphocyte transformation [13].
• Clofazimine does not cross the blood-brain barrier, but does cross the placenta, and is found in human breast milk [12].

Associations of Lamprene with other chemical compounds

• Double-blind, randomized, controlled clinical trial of clofazimine compared with chloroquine in patients with systemic lupus erythematosus [19].
• In vitro screening of three-drug combinations showed that combinations of roxithromycin, ethambutol, and a third potential anti-M. avium drug (rifampin, amikacin, ofloxacin, or clofazimine) resulted in further enhancement of activity in 13 out of 20 drug combinations screened [20].
• The objective of this study was to investigate the relationship between the antimycobacterial properties of the antileprosy drug clofazimine and its stimulatory effect on the release of reactive oxidants by polymorphonuclear leukocytes by using a variety of phenazine derivatives [21].
• It is proposed that the inhibitory mechanism of action of clofazimine is to scavenge chlorinating oxidants generated by the MPO-Cl(-)-H2O2 system, while dapsone converts MPO into its inactive compound II (ferryl) form [22].
• A phase II evaluation of clofazimine plus doxorubicin in advanced, unresectable primary hepatocellular carcinoma [23].

Gene context of Lamprene

• HPLC analyses suggested that the drugs were not significantly metabolized in the MPO-H2O2 system in the absence of Cl-. Bleaching of clofazimine was stimulated by Cl- in the MPO system, suggesting the involvement of HOCl [22].
• Furthermore, TNF-alpha potentiates the pro-oxidative effects of clofazimine and its analogues on PMNL [24].
• In addition, treatment of infected mice with either IFN-gamma or liposomal clofazimine significantly reduced the infection in peritoneal macrophages [25].
• We have used a phospholipase C (PLC)-deletion mutant (plcABC) of the H37Rv strain of Mycobacterium tuberculosis (MTB), as well as a plcA-insertion mutant of Mycobacterium smegmatis, to investigate the possible involvement of PLCs in clofazimine-mediated inhibition of mycobacterial K(+) transport and growth [26].
• METHODS: The ceoB and ceoC genes of MTB, which encode the TrkA proteins, CeoB and CeoC, were deleted by homologous recombination, and the double-knockout mutant and wild-type strains compared with respect to K+ uptake and growth in the presence and absence of clofazimine (0.015-2.5 mg/L) using radioassay procedures [27].

Analytical, diagnostic and therapeutic context of Lamprene

• From the perspective of the chemotherapy of MAC infections, the present findings indicate an important possibility that certain antimycobacterial drugs, such as rifamycins (RIF and RFB), INH, CLO, and also some types of fluoroquinolones, may interfere with the ROI-mediated antimicrobial mechanisms of host MPhis against intracellular MAC organisms [28].
• After treatment for 4 weeks, the large quantities of clofazimine that had accumulated in the organs of mice seriously interfered with the enumeration of the CFU and assessment of the efficacy of the treatment [29].
• When Clofazimine was administered to athymic mice bearing WIL as a subcutaneous xenograft, tumour growth rate was significantly reduced, so that after 3 weeks, tumour size was one third that of controls (p < 0.01) [14].
• With the knowledge of this rare condition caused by clofazimine, appropriate management to avoid an unnecessary laparotomy is possible [30].
• Clofazimine crystals are red in the frozen section and exhibit bright-red birefringence [30].

References