STUDIES ON THE METABOLIC FATE OF 14C-ROKITAMYCIN: I. ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION IN RATS

Blood concentrations of 14C-rokitamycin (14C-TMS-19-Q) reached their peaks at 1 hour after a single oral (200 mg/kg) administration to male and female rats, and they were 28.0±0.8 and 24.9±2.0 μg/ml, respectively. No significant differences were observed between male and female in AUC values or maximum blood concentrations. The distribution of TMS-19-Q was good, and concentrations of 14C were high in liver, kidney, spleen, pancreas, adrenal, pituitary gland, thyroid, trachea, exorbital lacrimal gland, submaxillary gland and bone marrow. During the 72 hours period after a single oral (200 mg/kg) administration of 14C-TMS-19-Q to male rats, 8.0 and 89.6% of the dose were excreted in urine and feces, respectively and a total recovery rate was 97.5% of the dose. During the 48 hours period after a single intraduodenal (200 mg/kg) administrationof 14CTMS-19-Q in male rats, 6.9 and 36.2% of the dose were excreted in urine and bile, respectively. Reabsorption of 14C excreted from the bile was negligible. Absorptions of TMS-19-Q from the duodenum, jejunum, ileum and colon were good, but absorption from the stomach was negligible. Major metabolic reactions of TMS-19-Q were deacylation and hydroxylation, and the major metabolites in rats of TMS-19-Q found in the plasma, urine and bile after oral and intraduodenal administration were 10-OH-TMS-19-Q, leucomycin AT, leucomycin V and 14-OH-leucomycin V.