Newell D R
Cancer Research Unit, University of Newcastle upon Tyne, U.K.
Ann Oncol. 1994;5 Suppl 4:9-14; discussion 15. doi: 10.1093/annonc/5.suppl_4.s9.
The exploitation of pharmacokinetic-pharmacodynamic relationships is worthwhile for drugs where there is difficulty or delay in obtaining clinical evidence of therapeutic or toxic effects, where there is a clear relationship between the pharmacokinetics and pharmacodynamics, and where the drug has a small therapeutic index. These criteria are amply met by cytotoxic anticancer agents. In particular, an extensive literature for all classes of cancer chemotherapeutics shows that the correlation between pharmacokinetic parameters (peak concentration, area under the plasma concentration-time curve, clearance or steady-state levels) and toxicity is in many cases better than the relationship between dose and toxicity. Adaptive dosing: Prospective studies of dose adaptation on the basis of pharmacokinetic or pharmacodynamic information, with or without feedback control, have shown that pharmacologically guided dosing is feasible. Adaptive dosing results in reduced pharmacokinetic variability and more consistent toxicity. Currently, there are insufficient prospective studies to allow conclusions concerning the efficacy of such a dosing system.
对于那些在获取治疗效果或毒性的临床证据方面存在困难或延迟、药代动力学和药效学之间存在明确关系且治疗指数较小的药物，利用药代动力学 - 药效学关系是值得的。细胞毒性抗癌药物充分满足这些标准。特别是，各类癌症化疗药物的大量文献表明，药代动力学参数（峰浓度、血浆浓度 - 时间曲线下面积、清除率或稳态水平）与毒性之间的相关性在许多情况下优于剂量与毒性之间的关系。适应性给药：基于药代动力学或药效学信息进行剂量调整的前瞻性研究，无论有无反馈控制，均表明药理指导下的给药是可行的。适应性给药可降低药代动力学变异性并使毒性更一致。目前，尚无足够的前瞻性研究来得出关于这种给药系统疗效的结论。
