Cano J P, Aubert C, Rigault J P, Gilli R, Coassolo P, Monjanel S, Seitz J F, Carcassone Y
Cancer Treat Rep. 1981;65 Suppl 3:33-42.
The use of pharmacokinetic studies for individual dose regimen adjustments in anticancer therapy is considered. The example of methotrexate in the treatment of head and neck tumors demonstrates the validity of this approach. Moreover, the importance of biotransformations of this antimetabolite is confirmed using a high pressure liquid chromatography assay. The example of 5-FU outlines the analytical and mathematical difficulties rendering this approach unlikely for routine use. Some preliminary relations between pharmacokinetic parameters (plasma clearance) and clinical response are presented. The determination of the main plasma metabolic 5-6 dihydro 5-FU by GC/MS and its possible role in the nonlinear pharmacokinetics of the drug in therapeutic failure are discussed.
考虑将药代动力学研究用于抗癌治疗中个体剂量方案的调整。甲氨蝶呤治疗头颈部肿瘤的例子证明了这种方法的有效性。此外，使用高压液相色谱分析法证实了这种抗代谢物生物转化的重要性。5-氟尿嘧啶的例子概述了分析和数学方面的困难，使得这种方法不太可能用于常规应用。文中给出了一些药代动力学参数（血浆清除率）与临床反应之间的初步关系。讨论了通过气相色谱/质谱法测定主要血浆代谢物5,6-二氢-5-氟尿嘧啶及其在治疗失败时药物非线性药代动力学中可能发挥的作用。
