Effect of renal dysfunction in dogs on the disposition and marrow toxicity of melphalan.
Effect of renal dysfunction in dogs on the disposition and marrow toxicity of melphalan.
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犬肾功能不全对马法兰的处置和骨髓毒性的影响。
DOI：
10.1038/bjc.1981.52
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发表时间：
1981
影响因子：
8.8
通讯作者：
Mason,NL
中科院分区：
文献类型：
--
作者：
Alberts,DS;Chen,HG;Benz,D;Mason,NL
肾功能衰竭对马法兰药理学和毒性的影响尚不清楚。这些信息很有趣，因为马法兰是治疗多发性骨髓瘤最常用的抗癌药物，多发性骨髓瘤通常与肾衰竭有关。我们研究了肾次全切除术诱导肾衰竭前后肠外马法兰在犬体内的分布和骨髓毒性。手术使肌酐清除率平均降低62%（P=0.001）。静脉注射美法仑 (1 mg/kg) 后的最低中性粒细胞计数在肾切除术前平均为 4.9 x 10 (3)/mm3，在肾切除术后平均为 0.9 x 10 (3)/mm3 (P= 0.002)。在肾切除术前的犬中，使用美法仑 (1 mg/kg) 后记录的平均最低血小板计数为 115 x 10 (3)/mm3，在肾切除术后的犬中为 9.7 x 10 (3/mm3) (P= 0.002)。肾切除术后，静脉注射美法仑的终末期血浆半衰期和肾脏清除率均提高 (P= 0.02)这些研究表明，在犬肾功能不全的情况下，静脉注射美法仑引起的骨髓抑制显着增加，并且其血浆消除和肾清除率显着降低。这些数据表明，当用于患有肾功能衰竭的骨髓瘤患者时，肠胃外美法仑的起始剂量应减少至少50%。
The effect of renal failure on melphalan pharmacology and toxicity has been poorly understood. Such information is of interest because melphalan is the most commonly used anticancer drug in the treatment of multiple myeloma, which is frequently associated with renal failure. We have studied the disposition and marrow toxicity of parenteral melphalan in dogs before and after induction of renal failure with subtotal nephrectomy. The surgical procedure decreased the creatinine clearance by an average of 62%(P= 0.001). The lowest neutrophil counts following iv melphalan (1 mg/kg) averaged 4.9 x 10 (3)/mm3 pre-nephrectomy and 0.9 x 10 (3)/mm3 post-nephrectomy, respectively (P= 0.002). The mean lowest recorded platelet counts after melphalan (1 mg/kg) were 115 x 10 (3)/mm3 in the pre-nephrectomized dogs, and 9.7 x 10 (3/mm3 in those who had been nephrectomized (P= 0.002). Following nephrectomy, iv melphalan's terminal-phase plasma half-life and renal clearance were both raised (P= 0.02) to 75% over pre-nephrectomy values. These studies show that iv melphalan-induced myelosuppression is markedly increased and its plasma elimination and renal clearance significantly decreased in the presence of renal dysfunction in dogs. These data suggest that parenteral melphalan's starting dose be decreased by at least 50% when used in myeloma patients with renal failure.
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口服马法兰动力学
DOI：
--
发表时间：
1979
期刊：
Clinical pharmacology and therapy
影响因子：
--
作者：
D. Alberts;Sai Y. Chang;H.;T. L. Evans;T. Moon
通讯作者：
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影响因子：
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作者：
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DOI：
--
发表时间：
1977
期刊：
Cancer treatment reports
影响因子：
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作者：
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