Zucchetti M, D'Incalci M, Willems Y, Cavalli F, Sessa C
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Cancer Chemother Pharmacol. 1988;22(1):87-9. doi: 10.1007/BF00254189.
Melphalan (L-PAM) pharmacokinetics were investigated in nine ovarian cancer patients before and after cisplatin (DDP) treatment. When L-PAM was given 24 h before DDP, the elimination half-life (t 1/2 beta), plasma clearance (Clp), and volume of distribution (Vd beta) of L-PAM were, respectively: 46.4 +/- 6.7 min, 20.5 +/- 3.7 l/m2, and 306.8 +/- 34.4 ml/min per square meter. When L-PAM was inoculated 24 h after DDP, t 1/2 beta, Clp, and Vd beta were 47.5 +/- 6.3 min, 20.4 +/- 2.8 l/m2, and 322.0 +/- 54.1 ml/min per square meter. Thus, DDP pretreatment does not significantly affect L-PAM pharmacokinetics. Regression analysis showed a significant correlation between the L-PAM elimination rate constant (beta) and renal function assessed by creatinine clearance. One patient who received this sequence of treatment for six courses showed a threefold decrease of L-PAM Clp after the last treatment. The reported high myelotoxicity of the combination of DDP and L-PAM when DDP was given 24 h before L-PAM cannot be attributed to DDP-induced changes in L-PAM kinetics but might to some extent be related to a loss of renal function consequent to many courses of treatment.
对9例卵巢癌患者在顺铂（DDP）治疗前后进行了美法仑（L-PAM）的药代动力学研究。当在DDP给药前24小时给予L-PAM时，L-PAM的消除半衰期（t 1/2β）、血浆清除率（Clp）和分布容积（Vdβ）分别为：46.4±6.7分钟、20.5±3.7升/平方米和306.8±34.4毫升/分钟每平方米。当在DDP给药后24小时接种L-PAM时，t 1/2β、Clp和Vdβ分别为47.5±6.3分钟、20.4±2.8升/平方米和322.0±54.1毫升/分钟每平方米。因此，DDP预处理对L-PAM的药代动力学没有显著影响。回归分析表明，L-PAM消除速率常数（β）与通过肌酐清除率评估的肾功能之间存在显著相关性。一名接受该治疗方案六个疗程的患者在最后一次治疗后L-PAM的Clp下降了三倍。当在L-PAM前24小时给予DDP时，报道的DDP与L-PAM联合使用时的高骨髓毒性不能归因于DDP诱导的L-PAM动力学变化，但可能在一定程度上与多个疗程治疗导致的肾功能丧失有关。
