Arpon David Rey, Gandhi Maher K, Martin Jennifer H
School of Medicine, University of Queensland, Princess Alexandra Hospital Campus, Woolloongabba, Australia; Translational Research Institute, Woolloongabba, Queensland, Australia.
Br J Clin Pharmacol. 2014 Aug;78(2):274-81. doi: 10.1111/bcp.12318.
The issue of tailored dosing adjusted according to a range of patient-specific factors other than bodyweight or body surface area is of large and increasing clinical and financial concern. Even if it is known that dosing alterations are likely to be required for parameters such as body composition, gender and pharmacogenetics, the amount of dosing change is unknown. Thus, pharmacokinetically guided dosing is making a resurgence, particularly in areas of medicine where there are cost constraints or safety issues, such as in haematology medications. However, the evidence to support the behaviour is minimal, particularly when long-term outcomes are considered. In haematology, there are particular issues around efficacy, toxicity and overall cost. Newer targeted agents, such as the monoclonal antibody rituximab and the tyrosine kinase inhibitor imatinib, whilst clearly being highly effective, are dosed on a milligram per square metre (rituximab) or fixed dose basis (imatinib), regardless of body composition, tumour aspects or comorbidity. This review questions this practice and raises important clinical issues; specifically, the clinical potential for combined pharmacokinetically and pharmacodynamically guided dosing of new targeted agents in haematological malignancies. This pharmacokinetically and pharmacodynamically guided dosing is an emerging area of clinical pharmacology, driven predominantly by toxicity, efficacy and cost issues, but also because reasonable outcomes are being noted with more appropriately dosed older medications adjusted for patient-specific factors. Clinical trials to investigate the optimization of rituximab dose scheduling are required.
根据除体重或体表面积之外的一系列患者特定因素调整给药剂量的问题，在临床和经济方面受到了极大且日益增长的关注。即使已知对于诸如身体组成、性别和药物遗传学等参数可能需要调整给药剂量，但剂量变化的幅度仍不明确。因此，药代动力学指导下的给药正在复兴，尤其是在存在成本限制或安全问题的医学领域，例如血液学药物。然而，支持这种做法的证据极少，尤其是在考虑长期结果时。在血液学中，围绕疗效、毒性和总体成本存在一些特殊问题。新型靶向药物，如单克隆抗体利妥昔单抗和酪氨酸激酶抑制剂伊马替尼，虽然显然非常有效，但给药是基于每平方米毫克数（利妥昔单抗）或固定剂量（伊马替尼），而不考虑身体组成、肿瘤情况或合并症。本综述对这种做法提出质疑并提出了重要的临床问题；具体而言，在血液系统恶性肿瘤中联合药代动力学和药效学指导下的新型靶向药物给药的临床潜力。这种药代动力学和药效学指导下的给药是临床药理学的一个新兴领域，主要由毒性、疗效和成本问题驱动，但也因为对根据患者特定因素调整剂量的 older 药物进行更合理给药时观察到了合理的结果。需要进行临床试验来研究利妥昔单抗剂量方案的优化。
