[Tissue distribution and deposition of clofazimine in mice following oral administration of isoniazid].

Yu Lu, Mei-Qin Zheng, Bin Wang, Wei-Jie Zhao, Lei Fu, Peng Li, Bo-Wen Liang, Nai-Hui Chu
Author Information
  1. Yu Lu: Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.

Abstract

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].
CONCLUSION: Concomitant administration of isoniazid reduced clofazimine levels significantly in fat tissues while resulted in an increase of its level in lung tissues.

MeSH Term

Adipose Tissue
Administration, Oral
Animals
Clofazimine
Isoniazid
Kidney
Liver
Mice
Mice, Inbred Strains
Tissue Distribution

Chemicals

Clofazimine
Isoniazid

Word Cloud

Created with Highcharts 10.0.0clofaziminemice+/-2monthsreceivingadministrationisoniazidfatmonthtissueslevel[1microg/gdosealone1microg/g]distributiondepositionfollowingmg/kgbodyweightsinglelungsmallintestinekidneyslevelslungshighestdrughighercomparedtissueconcomitantsignificantlyOBJECTIVE:TissueinvestigatedwithoutMETHODS:Kunminggivensuspensionorallydaily13either25Tissuesliverspleenpooledplasmaanalyzedtreatedgroupshigh-performanceliquidchromatographyRESULTS:spleensliverscontinuouslyalsocontinuoussamples57117349microg/g]than3284712lower2893027511943353527158CONCLUSION:Concomitantreducedresultedincrease[Tissueoralisoniazid]

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