PHYSIOLOGICAL DISPOSITION, SUBCELLULAR DISTRIBUTION AND TISSUE BINDING OF α‐CHACONINE (3H)12

Abstract

The distribution, absorption, metabolism and tissue binding of radioactivity were studied in hamsters after oral and intraperitoneal administration of α‐chaconine‐(3H). The material was well absorbed from the gastrointestinal tract and nearly 25% of the label was excreted in 7 days via urine and feces. The excretion was higher in urine (24%) than in feces (1%). Tissue concentrations of radioactivity peaked at 12 h following po administration, with the highest concentrations being in lungs, liver, spleen, skeletal muscle, kidney and pancreas, with heart and brain containing moderate amounts. Excretion of chloroform‐soluble products in the feces was 100 higher than that of chloroform‐insoluble metabolites after oral and ip administration. In urine, the activity was predominantly in the chloroform‐insoluble form and the chloroform‐soluble metabolites were relatively small in amounts (0.29, 0.85 and 2.45% versus 0.0, 0.14 and 0.19 for 12, 24 and 72 h, respectively). After 7 days, the chloroform‐soluble metabolites in urine increased to 20% of the excreted radioactivity, while the amount of chloroform‐insoluble metabolites was less than 1%. Subcellular distribution of the labeled compound indicated the highest concentration of radioactivity in the nuclear and microsomal fractions of brain, liver, and heart tissues. Binding of radioactivity was observed in brain, testes, kidney, lung, liver and heart. All of the label in brain appeared to be in bound form. The results indicated that α‐chaconine which is absorbed from the gastrointestinal tract after oral administration persists in various tissues, much of it in bound (nonextractable) form (in microsomal fraction).