Suzuki T, Sakai A, Morishita M, Muranishi S
Jpn J Antibiot. 1987 Mar;40(3):519-30.
After a consecutive oral administration of 200 mg/kg/day of 14C-rokitamycin (TMS-19-Q) daily for 28 days to male rats, the accumulation of radioactivity in tissues and its disappearance after the cessation of the administration was studied. Blood concentrations at peak times and 24 hours after each administration were determined daily. Both values increased gradually until the 14th day and thereafter remained roughly constant. The extent of elimination of radioactivity from the blood was practically not affected by the consecutive administration. Affinities of radioactivity to the liver, kidney, spleen, adrenal, pituitary gland, preputial gland, thyroid, intraorbital lacrimal gland and bone marrow were comparatively higher than those to other tissues. Tissue concentrations in the above mentioned tissues at the 1st day after the completion of consecutive administrations for 14 and 28 days were 2.6-6.1 and 3.2-6.8 times higher, respectively, than those at the 1st day after a single administration. The elimination of radioactivity from the tissue after the consecutive administration for 28 days was slightly slower than that after a single administration. In the consecutive daily administration for 28 days, the metabolic fate of radioactivity reached a steady state after 14 days of consecutive daily administration. Hence, the accumulation of the radioactivity did not particularly occurred. During the consecutive administration, recoveries of radioactivity in the urine and feces were almost at a constant rates, with 8.0 and 93.8% of the total radioactivity given excreted in the urine and feces, respectively, within 10 days after the last administration.
对雄性大鼠连续28天每天口服给予200mg/kg/天的14C-罗他霉素(TMS-19-Q)后,研究了组织中放射性的蓄积情况及其给药停止后的消失情况。每天测定每次给药后峰值时间和24小时时的血药浓度。两者的值在第14天前逐渐升高,此后大致保持恒定。连续给药对血液中放射性的消除程度实际上没有影响。放射性对肝脏、肾脏、脾脏、肾上腺、垂体、包皮腺、甲状腺、眶内泪腺和骨髓的亲和力相对高于对其他组织的亲和力。连续给药14天和28天结束后第1天,上述组织中的组织浓度分别比单次给药后第1天高2.6 - 6.1倍和3.2 - 6.8倍。连续给药28天后组织中放射性的消除比单次给药后略慢。在连续28天每日给药中,连续每日给药14天后放射性的代谢命运达到稳定状态。因此,放射性没有特别蓄积。在连续给药期间,尿液和粪便中放射性的回收率几乎恒定,末次给药后10天内,尿液和粪便中分别排泄了给予的总放射性的8.0%和93.8%。