Tissue Distribution and Deposition of Clofazimine in Mice Following Oral Administration with or without Isoniazid

Abstract

Tissue distribution and deposition of clofazimine (CAS 2030-63-9) in mice were investigated following administration of clofazimine with or without isoniazid (CAS 54-85-3). Balb/c mice were administered clofazimine suspension in mustard oil orally at a daily dose of 20 mg/kg body weight either alone or along with isoniazid (10 mg/kg body weight) for 15 or 30 days. Various tissues (liver, lung, spleen, small intestine, heart, kidneys, mesentric fat, foot pad and nerve) and pooled plasma were analysed for clofazimine in all the treated groups. High levels of clofazimine were observed in tissues having reticulo-endothelial components (53-263 microg/g wet tissue). In other tissues the levels of the drug were relatively lower (8.1-42.8 microg/g of wet tissue). There was a significant amount of the drug in foot pads and pooled nerve tissue showed detectable amount of the drug. The plasma concentrations in all treated groups were in the range of 0.5-0.8 microg/ml. Tissue levels were found to be increased in selective tissues with the length of drug administration. Concomitant administration of isoniazid reduced clofazimine levels significantly in tissues like small intestine, spleen, and foot pad and resulted in an increase in plasma levels.