The pharmacokinetics of daunomycin in man
The pharmacokinetics of daunomycin in man
复制标题
道诺霉素在人体内的药代动力学
DOI：
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发表时间：
1971
期刊：
影响因子：
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通讯作者：
J. Holtzman
中科院分区：
文献类型：
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作者：
D. Alberts;N. Bachur;J. Holtzman
通过使用荧光测定方法，测定了接受该药物治疗的播散性实体恶性肿瘤患者中道诺霉素及其荧光代谢物的血浆水平、尿液排泄物和组织水平。患者接受单次快速静脉注射道诺霉素 80 mg。每平方米120毫克。每平方米。荧光研究显示血浆半衰期短为0.75小时，血浆半衰期长为55小时，表观分布容积约为1000升，相对分布容积为每平方米580升。 7 天内，尿液中的药物和荧光代谢物平均占总剂量的 13% 至 14%。使用氚化道诺霉素，但同位素测定产生的值与荧光测定不同。这些被解释为氚交换或道诺霉素代谢的结果。给药后16和19小时尸检标本中检测到道诺霉素荧光，其中肾、脾、肝和肺中含量最高。从血浆和尿液中提取的荧光物质主要由道诺霉素 (D1) 和道诺霉素代谢物 (D2) 组成，但也检测到少量糖苷配基。由于道诺霉素的半衰期较长，建议将目前的治疗方案修改为单次静脉注射。
Through the use of fluorescence assay methods, the plasma levels, urinary excretion, and tissue levels of daunomycin and its fluorescent metabolites were determined in patients treated with this drug for disseminated solid malignancies. The patients received daunomycin in a single rapid intravenous dose at 80 mg. per square meter and 120 mg. per square meter. Fluorescence studies showed the short plasma half‐life to be 0.75 hours, the long plasma half‐life to be 55 hours, the apparent volume of distribution to be ab out 1,000 L., and the relative volume of distribution to be 580 L. per square meter. Drug and fluorescent metabolites in urine averaged 13 to 14 per cent of the total dosage in 7 days. Tritiated daunomycin was used, but isotopic assay produced values different from those with fluorescence assay. These were interpreted to be the result of tritium exchange or metabolism of the daunomycin. Daunomycin fluorescence was detected in autopsy specimens 16 and 19 hours after administration, with the highest levels in kidney, spleen, liver, and lung. The fluorescent species extracted from both plasma and urine consisted predominantly of daunomycin (D1) and daunomycin metabolite (D2), although small amounts of the aglycones were detected. It is proposed that, because of the long half‐life of daunomycin, the current treatment schedule be revised to a single intravenous dose.