Galpin A J, Evans W E
Pharmaceutical Department, St. Jude Children's Research Hospital, Memphis, TN 38101-0318.
Clin Chem. 1993 Nov;39(11 Pt 2):2419-30.
Several anticancer drugs display characteristics that make them suitable candidates for therapeutic drug monitoring (TDM), including substantial pharmacokinetic variability and a narrow therapeutic index. However, concentration-effect relationships (pharmacodynamics) of most antineoplastic agents have not been well defined, thus limiting the widespread clinical application of TDM for cancer chemotherapy. Strategic incorporation of pharmacokinetic studies during phase I-III clinical trials should facilitate the identification of concentration-effect relationships and the definition of clinically useful levels of treatment intensity. We review representative clinical studies that have defined pharmacodynamic relationships for methotrexate, teniposide, etoposide, carboplatin, and mercaptopurine. Given that TDM has impacted positively on the clinical use of many drugs belonging to other therapeutic classes, and that pharmacodynamic correlations have been identified in several recent studies of anticancer drugs, we consider implementation of TDM a rational strategy for optimizing the use of selected antineoplastics.
几种抗癌药物具有一些特性，使其成为治疗药物监测（TDM）的合适候选药物，这些特性包括显著的药代动力学变异性和较窄的治疗指数。然而，大多数抗肿瘤药物的浓度-效应关系（药效学）尚未得到很好的界定，因此限制了TDM在癌症化疗中的广泛临床应用。在I-III期临床试验期间战略性地纳入药代动力学研究，应有助于确定浓度-效应关系，并明确临床有用的治疗强度水平。我们回顾了一些代表性的临床研究，这些研究确定了甲氨蝶呤、替尼泊苷、依托泊苷、卡铂和巯嘌呤的药效学关系。鉴于TDM已对许多其他治疗类别的药物的临床应用产生了积极影响，并且在最近几项抗癌药物研究中已确定了药效学相关性，我们认为实施TDM是优化某些抗肿瘤药物使用的合理策略。
