Bone distribution study of anti leprotic drug clofazimine in rat bone marrow cells by a sensitive reverse phase liquid chromatography method

Mechanisms of action and therapeutic efficacies of the lipophilic antimycobacterial agents clofazimine and bedaquiline

“…32,39,94,104 The fat-tissues include macrophage-rich organs such as the lungs, livers, spleen, brain 110 and the bone marrow. [111][112][113] As mentioned above, the drug has a long half-life of approximately 70 days, which contributes to skin discolouration, its most frequent AE. 75 During its long-term tissue accumulation, clofazimine undergoes xenobiotic sequestration resulting in the formation of crystal-like drug inclusions (CLDI) in the cytoplasm of tissue macrophages.…”

Outcome of the public consultation on the draft opinion providing clarification of some aspects related to genotoxicity assessment

“…This confirms the good perfusion of bony structures with the circulating blood and should enable compounds to be deposited in bone relatively quickly after exposure (6). In addition, numerous compounds have been detected in both bone marrow and blood (see below for examples), which supports the use of blood as a surrogate for bone marrow exposure Compounds detected in bone marrow and in blood (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) Acetaminophen, Alprazolam, Amitriptyline, Amobarbital, Amphetamine, Bromazepam, Bromoisoval, Carbamazepine, Chlorpheniramine, Chlorpromazine, Clofazimine single oral dose of 20mg/kg, the maximum concentration of CLF in plasma and bone marrow cells were obtained at 12h with the concentrations of 593.2 and 915.4 ng/mL, respectively., Clomipramine,Clopidogrel,Cocaine,Codeine,Dalbavancin,Daunomycin,Desipramine,Diazepam,Diphenhydramine,Dosulepin,Doxepin,Endosulfan,Estazolam,Ethanol,Flurazepam,Imipramine,Levomepromazine,Lidocaine,Mexiletine,Methamphetamine,Methylephedrine,Midazolam,Mirtazapine,Moclobemide,Morphine,Nortriptyline,Olanzapine,Paraquat,Paroxetine,Phenobarbital,Propofol,Pentobarbital,Promethazine,Secobarbital,…”

Simultaneous determination of the potent anti-tuberculosis regimen—Pyrazinamide, ethambutol, protionamide, clofazimine in beagle dog plasma using LC–MS/MS method coupled with 96-well format plate

“…Different solvent systems such as ACN and MeOH with various buffers like ammonium acetate and ammonium formate in different pH and different flow rates were tried meticulously. The several columns at different length or inner diameters, such as Inertsil ODS3 C18 column [25], Ailgent ZORBAX SB-C18 column, Atlantis dC18 column [26], Phenomenex Luna RP-C18 column [27], were applied to this assay for the suitable retention time and separation. Finally, an Agilent SB-Aq column was selected to conduct this assay coming to terms with a suitable chromatographic behavior.…”

“…To date, numerous analytical methods have been used for anti-TB drugs determination alone or in combination. Yet, the established methods suffer in some cases from the limited quantitative range, tedious sample preparation, huge sample volume, which make them less suitable for routine application [[25], [26], [27], [28]]. However, in consideration of the huge dispersion in physicochemical property of the compounds in this new regimen, it is also a big challenge to obtain suitable chromatographic behaviors on a single chromatographic column with tiny bio-sample volume during one LC or LC–MS/MS loop.…”