Pharmacy Department, Sultan Qaboos University Hospital, Muscat, Oman.
Department of Hematology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
J Oncol Pharm Pract. 2021 Apr;27(3):693-701. doi: 10.1177/1078155220979048. Epub 2020 Dec 10.
Most anticancer agents show wide variability in pharmacokinetics (PK) and have a narrow therapeutic index which makes fixed dosing suboptimal. To achieve the best therapeutic outcomes with these agents, many studies have postulated using PK or therapeutic drug monitoring (TDM)-guided dosing. However, multiple factors contribute to the variability in PKs making the application of TDM in practice challenging. Also, despite the known association with clinical outcomes, standard guidelines on PK-guided dosing are lacking for most agents. Understanding the factors that contribute to PK variability and their impact is essential for dose individualization. The purpose of this review is to discuss the factors that contribute to the PK variability of anticancer agents and the challenges faced in practice when individualizing doses for certain widely used agents. Searching the literature has identified several gaps and efforts are needed to ensure better targeting of cancer therapeutics.
大多数抗癌药物在药代动力学(PK)方面表现出很大的变异性,并且治疗指数较窄,这使得固定剂量不太理想。为了用这些药物获得最佳的治疗效果,许多研究假设使用 PK 或治疗药物监测(TDM)指导剂量。然而,多种因素导致 PK 的变异性,使得 TDM 在实践中的应用具有挑战性。此外,尽管与临床结果有明确的关联,但大多数药物的 PK 指导剂量的标准指南仍然缺乏。了解导致 PK 变异性的因素及其影响对于剂量个体化至关重要。本文的目的是讨论导致抗癌药物 PK 变异性的因素,以及在为某些广泛使用的药物进行剂量个体化时在实践中面临的挑战。文献检索发现了几个空白点,需要努力确保更好地针对癌症治疗药物。