Tissue pharmacokinetics and inhibition of DNA synthesis in mice treated with sporamycin.

Abstract

Examination of blood and organ concentrations of sporamycin in normal mice showed a rapid decrease of sporamycin from peripheral blood and a high level of sporamycin in urine 10 minutes after intravenous injection of the antibiotic. At the same time, the highest level was found in the kidneys and low levels were found in the lungs and spleen. When sporamycin was added to mouse organ homogenate at 37 degrees C, remarkable inactivation of sporamycin by the homogenate of the liver, kidney, testis, etc., was noted but this inactivation was slight by tumor homogenate. Sporamycin inhibited the tritiated thymidine incorporation into DNA of normal tissues, but a different pattern of inhibition and recovery on the incorporation of 3H-TdR into DNA was observed among mouse organs. It was noted that the antibiotic may damage normal tissues in spite of a rapid excretion and inactivation of sporamycin in mice, but this damage was recovered rapidly within 1 approximately 2 days after the treatment.