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Biodistribution of Radiolabeled [ 3 H] CMT-3 in Rats

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CMT-3 is a NON-ANTIMICROBIAL tetracycline (TC), chemically modified to enhance its collagenase-inhibitory property. This property is therapeutically useful in treating diseases such as periodontitis, cancer and arthritis. CMT-3 was labeled with tritium ( 3 H) at Carbon 7. Four adult male Sprague-Dawley rats (350-400 g body weight) were gavaged once with a mixture of cold CMT-3 and ( 3 H) CMT-3 (750 mu Ci). An additional four rats were gavaged for 2 days with cold CMT-3(15 mg/Kg/day) and on the third day the rats were gavaged with a mixture of cold and (3 H) CMT-3 (750 mu Ci) and all 8 rats were placed in the metabolic cages. Blood samples were collected from the tail at multiple intervals from 1-14 hr after ( 3 H) CMT-3 administration. At 14 hr, the rats were anesthetized, euthanized and various tissues including visceral organs were removed and weighed. The contents of GI tracts were emptied and added to the fecal pellets and weighed. The urine samples were collected and volume measured. Each tissue or organ was minced finely with scissors and 100 mg of tissue was digested in 1 ml of Tissue-solv (Packard Lab), for 4 hrs at 37 o C and each sample was diluted up to 10 ml of distilled water. A 100 ml aliquot was taken and diluted with an equal volume of glacial acetic acid, 10 ml of Atom-lite was added and counted for radioactivity in a liquid scintillation spectrometer. This biodistribution study revealed that over 14 hrs, 54 percent and 3 percentof ( 3 H) CMT-3 were excreted in the feces and urine, respectively. The serum ( 3 H) CMT-3 count reached its maximum value at about 12 hours. The tissues retained the CMTs as follow: muscle (23percent); skin (2.41percent); bone (1.72percent); and the brain retained 0.21percent of the label. The radioactive CMT-3 in the visceral organs is as follows: GI tract - its contents (8.9percent); heart (0.41percent), testis (0.41percent); lungs greater than(0.16percent); spleen (0.08percent); liver (0.03percent); kidneys greater than (0.02percent).

Keywords: CMT 3 administratio; Non antimicrobial tetracycline; Radiolabeled CMT 3; experimental peridontitis; pharmacokinetics studies

Document Type: Review Article


Publication date: February 1, 2001

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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