Suzuki T, Sakai A, Morishita M, Muranishi S
Jpn J Antibiot. 1987 Mar;40(3):499-518.
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 micrograms/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) administration of 14C-TMS-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 A7, leucomycin V and 14-OH-leucomycin V.
对雄性和雌性大鼠单次口服（200mg/kg）14C-罗他霉素（14C-TMS-19-Q）后，血药浓度在1小时达到峰值，雄性和雌性大鼠的血药浓度分别为28.0±0.8和24.9±2.0μg/ml。雄性和雌性大鼠的AUC值和最大血药浓度未见显著差异。TMS-19-Q分布良好，肝脏、肾脏、脾脏、胰腺、肾上腺、垂体、甲状腺、气管、眶外泪腺、颌下腺和骨髓中14C浓度较高。雄性大鼠单次口服（200mg/kg）14C-TMS-19-Q后的72小时内，分别有8.0%和89.6%的剂量经尿液和粪便排泄，总回收率为给药剂量的97.5%。雄性大鼠单次十二指肠内给药（200mg/kg）14C-TMS-19-Q后的48小时内，分别有6.9%和36.2%的剂量经尿液和胆汁排泄。胆汁中排泄的14C重吸收可忽略不计。TMS-19-Q在十二指肠、空肠、回肠和结肠的吸收良好，但在胃中的吸收可忽略不计。TMS-19-Q的主要代谢反应为脱酰基和羟基化，口服和十二指肠内给药后，血浆、尿液和胆汁中TMS-19-Q在大鼠体内的主要代谢产物为10”-OH-TMS-19-Q、柱晶白霉素A7、柱晶白霉素V和14-OH-柱晶白霉素V。
