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为了给肿瘤临床合理用药提供依据,本文利用~3H同位素示踪法,研究了阿克拉霉素(ACM-B)的药代动力学。将~3H-ACM-B分别静注昆明种正常小鼠、荷S180肉瘤昆明种小鼠、P388白血病DBA/2种小鼠及Lewis肺癌C57BL/6种小鼠。测得不同时间血中放射性数据,作了药代动力学分析,说明药物由中央室向周边室转运较为迅速,反之转运较缓慢,消除速率常数为0.198小时~(-1),提示药物通过代谢和排泄后,消除较慢,有一定的蓄积性。 分布实验表明,肝中~3H-ACM-B摄取率最高,肺居第二位,其次为肾、脾。肿瘤对药物摄取并不高,但是保留时间较长,Lewis肺癌比其它两种实体瘤摄取率高。药物分布特点是:进入组织很快、分布较广、消除较慢。 排泄实验给药24小时后,测得粪中放射性为尿中的4倍,提示该药主要经胃肠道排泄。72小时粪尿排出放射性占总剂量的27％,进一步说明药物在体内消除缓慢。 综上所述,ACM-B药代动力学分析结果,基本能反映药物在小鼠体内的实际过程,因此认为,以二房室模型来描述本品的药一时曲线动态规律较合适。
In order to provide a basis for the rational clinical use of tumor, this paper studied the pharmacokinetics of aclacinomycin (ACM-B) by ~ 3H isotope tracing method. Kunming normal mice, S180 sarcoma Kunming mice, P388 leukemia DBA / 2 mice and Lewis lung carcinoma C57BL / 6 mice were intravenously injected with ~ 3H-ACM-B respectively. Measured at different times of radioactive blood data, made a pharmacokinetic analysis, indicating that the drug from the central chamber to the peripheral compartment more rapid transport, on the contrary slower transport, the elimination rate constant of 0.198 hours (-1), suggesting that the drug through the metabolism And after excretion, eliminate slowly, have some accumulation. The distribution experiment showed that the uptake rate of ~ 3H-ACM-B in the liver was the highest, followed by the lungs, followed by the kidney and spleen. Tumor uptake of drugs is not high, but the retention time longer, Lewis lung cancer uptake rate than the other two solid tumors. Drug distribution is characterized by: into the organization quickly, widely distributed, to eliminate slower. Excretion experiment 24 hours after administration, measured fecal radioactivity in urine 4 times, suggesting that the drug is mainly excreted by the gastrointestinal tract. 72 hours of excretion of radioactive radioactive accounted for 27% of the total dose, further illustrating the drug in the body to eliminate slowly. In summary, ACM-B pharmacokinetic analysis of the results can basically reflect the actual process of the drug in mice, so that the two-compartment model to describe the product of the drug’s temporal curve of the dynamic law is more appropriate.