STUDIES ON ORGAN DISTRIBUTION, ABSORPTION AND EXCRETION OF PEPLEOMYCIN SULFATE (NK631)

Abstract

1. Organ distribution of pepleomycin (NK631) in mice and rats was studied. NK631 was found at higher levels than bleomycin (BLM) in skin, lung, stomach, solid tumor, etc. in mice and rats.
Furthermore NK631 was detected in the mesenteric and lumbar lymph node, esophagus and prostate in rats and also distributed at about twice as high levels as BLM in the AH109A hepatoma cellmetastasized lymph nodes.
2. For the elucidation of reason on low pulmonary toxicity of NK631 which is in spite of 1.5 times highly disttibution in lung compared with BLM, inaetivation of various BLMs by high molecular fraction of lung of mice and rats was determined. The order of inactivation rate of various BLMs in lung was as follows: BLM-M5196>NK631>BLM>BLM-HPE. There is an encouraging coincidence between index of pulmonary fibrosis in mice and inactivating rate in lung.
3. A comparative study on the serum level and urinary excretion of NK631 and BLM was performed in dogs. The blood level and urinary excretion rate of both drugs were ahnost similar.
4. The blood levels of NK631 were comparable to those of BLM in cancer patients.