Biodistribution of radiolabeled [H-3] CMT-3 in rats

CMT-3 is a NON-ANTIMICROBIAL tetracycline (TC), chemically modified to enha nce its collagenase-inhibitory property. This property is therapeutically u seful in treating diseases such as periodontitis, cancer and arthritis. CMT -3 was labeled with tritium [H-3] at Carbon 7. Four adult male Sprague-Dawl ey rats (350-400 g body weight) were gavaged once with a mixture of cold CM T-3 and [H-3] 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 gava ged with a mixture of cold and [H-3] CMT-3 (750 mu Ci); and all 8 rats were placed in the metabolic cages. Blood samples Mere collected from the tail at multiple intervals from 1-14 hr alter [H-3] CMT-3 administration. At 14 hr, the rats were anesthetized, euthanized and various tissues including vi sceral organs were removed and weighed. The contents of GI tracts were empt ied and added to the fecal pellets and weighed. The urine samples were coll ected and volume measured. Each tissue or organ was minced finely with scis sors and 100 mg of tissue was digested in 1 mi of Tissue-solv (Packald Lab) , for 4 hrs at 37 degreesC and each sample was diluted up to 10 mi of disti lled water. A 100 mul aliquot was taken and diluted with an equal volume of glacial acetic acid, 10 mi of Atom-lite was added and counted for radioact ivity in a liquid scintillation spectrometer. This biodistribution study re vealed that over 14 hrs, 54% and 3% of [H-3] CMT-3 were excreted in the fec es and urine, respectively. The serum [H-3] CMT-3 count reached its maximum value at about 12 hours. The tissues retained the CMTs as follow: muscle ( 23%); skin (2.41%); bent: (1.72%); and the brain retained 0.21% of the labe l. The radioactive CMT-3 in the visceral organs is as follows: Gl tract - i ts contents (8.9%); heart (0.41%), testis (0.41%); lungs >(0.16%); spleen ( 0.08%); liver (0.03%); kidneys > (0.02%).