Lu Yu, Zheng Mei-Qin, Wang Bin, Zhao Wei-Jie, Fu Lei, Li Peng, Liang Bo-Wen, Chu Nai-Hui
Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2009 Sep;32(9):694-7.
Tissue distribution and deposition of clofazimine in mice were investigated following administration of clofazimine with or without isoniazid.
Kunming mice were given clofazimine suspension orally at a daily dose of 13 mg/kg body weight either alone or with isoniazid (25 mg/kg body weight) for a single dose or for 1 or 2 months. Tissues (liver, lung, spleen, small intestine, kidneys, fat) and pooled plasma were analyzed for clofazimine in all the treated groups by high-performance liquid chromatography.
The levels of clofazimine in fat tissues, kidneys, spleens, livers, lungs and small intestine were the highest in mice receiving the drug continuously for 2 months, and were also higher in mice receiving the drug for 1 month as compared to mice receiving a single dose administration. After continuous administration for 1 or 2 months, the clofazimine level was the highest in fat tissues as compared to other tissue samples. The clofazimine level in the lungs was higher in mice receiving concomitant administration of isoniazid [1 month (57 +/- 11) microg/g, 2 months (73 +/- 49) microg/g]than in those receiving clofazimine alone [1 month (32 +/- 8) microg/g, 2 months (47 +/- 12) microg/g], but the clofazimine level in the fat tissue was significantly lower in mice receiving concomitant isoniazid [1 month (289 +/- 30) microg/g, 2 months (275 +/- 119) microg/g], than in those receiving clofazimine alone [1 month (433 +/- 53) microg/g, 2 months (527 +/- 158) microg/g].
Concomitant administration of isoniazid reduced clofazimine levels significantly in fat tissues while resulted in an increase of its level in lung tissues.
研究在给予或未给予异烟肼的情况下，氯法齐明在小鼠体内的组织分布及沉积情况。
将昆明小鼠分为单独给予氯法齐明混悬液（每日剂量为13mg/kg体重）组、同时给予氯法齐明（13mg/kg体重）和异烟肼（25mg/kg体重）组，给药方式分为单次给药、给药1个月或给药2个月。采用高效液相色谱法分析所有处理组小鼠的组织（肝脏、肺、脾脏、小肠、肾脏、脂肪）及混合血浆中的氯法齐明含量。
连续给药2个月的小鼠脂肪组织、肾脏、脾脏、肝脏、肺和小肠中的氯法齐明含量最高，且给药1个月的小鼠上述组织中的氯法齐明含量高于单次给药的小鼠。连续给药1或2个月后，脂肪组织中的氯法齐明含量高于其他组织样本。同时给予异烟肼的小鼠肺组织中氯法齐明含量高于单独给予氯法齐明的小鼠[给药1个月：（57±11）μg/g，给药2个月：（73±49）μg/g vs 单独给予氯法齐明：给药1个月：（32±8）μg/g，给药2个月：（47±12）μg/g]，但同时给予异烟肼的小鼠脂肪组织中氯法齐明含量显著低于单独给予氯法齐明的小鼠[给药1个月：（289±30）μg/g，给药2个月：（275±119）μg/g vs 单独给予氯法齐明：给药1个月：（433±53）μg/g，给药2个月：（527±158）μg/g]。
同时给予异烟肼可使氯法齐明在脂肪组织中的含量显著降低，而在肺组织中的含量升高。
