Kinetics of intravenous melphalan
Kinetics of intravenous melphalan
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静脉注射马法兰的动力学
DOI：
10.1002/cpt197926173
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发表时间：
1979
影响因子：
6.7
通讯作者：
Joseph Gross
中科院分区：
文献类型：
--
作者：
D. Alberts;Sai Y. Chang;H.;T. Moon;T. L. Evans;R. Furner;K. Himmelstein;Joseph Gross
我们研究了9例癌症患者静脉注射美法仑后的处置和消除。使用高压液相色谱法和14 C-美法仑测定血浆和尿液中的药物浓度。8例患者的复合血浆t1/2 β为7.7 ± 3.3，t1/2 β为108 ± 20.8 min。美法仑的平均24小时尿排泄量为给药剂量的13.0 ± 5.4%。在2例患者中，在每个研究间隔（给药后24小时），血浆和尿液样本中80%至100%的14 C测量值可由母体化合物、单羟基和二羟基产物以及甲醇不可提取放射性的总和（即，蛋白结合活性）。这些数据和在体外37°下从血浆中快速消失的证据表明，自发降解而非酶代谢是体内美法仑t1/2 β的主要决定因素。
We have studied the disposition and elimination of melphalan after intravenous administration in 9 patients with cancer. High‐pressure liquid chromatography and 14C‐melphalan were used to assay drug concentration in plasma and urine. Composite plasma t½β was 7.7 ± 3.3 and t½β was 108 ± 20.8 min for 8 of the patients. The mean 24‐hr urinary excretion of melphalan was 13.0 ± 5.4% of the administered dose. In 2 patients, 80% to 100% of the measured 14C counts in plasma and urine samples at each study interval, up to 24 hr after drug administration, could be accounted for by the sum of parent compound, monohydroxy and dihydroxy products, and methanol nonextractable radioactivity (i.e., protein‐bound activity). These data and evidence of rapid disappearance from plasma at 37° in vitro suggest that spontaneous degradation, and not enzymatic metabolism, is the major determinant of the t½β of melphalan in vivo.