[Tissue distribution and deposition of clofazimine in mice following oral administration of isoniazid].
OBJECTIVE
Tissue distribution and deposition of clofazimine in mice were investigated following administration of clofazimine with or without isoniazid.


METHODS
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.


RESULTS
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].


CONCLUSIONS
Concomitant administration of isoniazid reduced clofazimine levels significantly in fat tissues while resulted in an increase of its level in lung tissues.
Lu
Yu
Y
Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
Zheng
Mei-Qin
MQ
Wang
Bin
B
Zhao
Wei-Jie
WJ
Fu
Lei
L
Li
Peng
P
Liang
Bo-Wen
BW
Chu
Nai-Hui
NH
D000273:Adipose Tissue / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D002991:Clofazimine / Q000493:pharmacokinetics*; D007538:Isoniazid / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D014018:Tissue Distribution
D002991:Clofazimine; D007538:Isoniazid