Comparative pharmacokinetics of chlorambucil and melphalan in man.

Comparative pharmacokinetics of chlorambucil and melphalan in man.
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苯丁酸氮芥和美法仑在人体中的药代动力学比较。

DOI:
10.1007/978-3-642-81488-4_16
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发表时间:
1980
期刊:
Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer
影响因子:
--
通讯作者:
Evans,TL
Evans,TL
中科院分区:
--
文献类型:
--
作者:
Alberts,DS;Chang,SY;Chen,HS;Larcom,BJ;Evans,TL

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我们研究了恶性血液病和实体瘤患者口服氯氨丁苯和马法兰的药代动力学。在标准口服剂量为0.6 mg/kg时,氯苯布坦的全身症状比马法兰快得多,其平均峰浓度和血浆消失曲线下面积比服用马法兰的患者大3-4倍。马法兰具有极不稳定的系统利用度,这是氯氨丁苯没有观察到的,也与片剂配方中的问题无关。百菌清对苯乙酸芥末有广泛的活性代谢,而马法兰则经历快速的化学降解,几乎没有活性代谢。在药代动力学的基础上,氯氨丁苯更大的体外稳定性,口服后更快速和可预测的系统利用度,以及极低的尿液排泄量,使其成为比马法兰更可预测的临床使用烷化剂,特别是对肾功能下降的患者。
We have studied the pharmacokinetics of orally administered chlorambucil and melphalan in patients with hematologic malignancies and solid tumors. With a standard oral dose of 0.6 mg/kg, chlorambucil showed much more rapid systemic appearance than did melphalan and had a mean peak plasma concentration and area under the plasma disappearance curve which was 3–4 times greater than that observed in patients receiving melphalan. Melphalan had extremely variable systemic availability which was not observed with chlorambucil, and was not related to problems in tablet formulation. Chlorambucil undergoes extensive active metabolism to phenylacetic acid mustard, whereas melphalan undergoes rapid chemical degradation and has little, if any, active metabolism. On a pharmacokinetic basis, chlorambucil’s greater in vitro stability, its more rapid and predictable systemic availability after oral dosing, and its extremely low urinary excretion make it a more predictible alkylating agent for clinical use than melphalan, especially for patients with reduced renal function.
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