Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Blood Cells Mol Dis. 2017 Sep;67:143-147. doi: 10.1016/j.bcmd.2017.08.007. Epub 2017 Aug 9.
Hydroxyurea is the primary pharmacotherapy to prevent complications of sickle cell anemia (SCA). Accumulated clinical experience across multiple age ranges has suggested that the use of an individualized maximum tolerated dose (MTD) will achieve optimal benefit of hydroxyurea treatment. However, the current empirical and trial-and-error approach for dose escalation often results in a lengthy titration process and is not strictly implemented in many clinics. Opportunities exist for pharmacokinetics model-based precision dosing of hydroxyurea to quickly achieve individual MTD. This review intends to introduce the use of a quantitative modeling approach including a Bayesian adaptive control strategy for the precision dosing of hydroxyurea. The rationale and practical considerations for the implementation of this approach are discussed. Future research directions with a focus on integrating specific safety and other clinical outcome endpoints into dose selection decision making are also discussed.
羟脲是预防镰状细胞贫血（SCA）并发症的主要药物治疗方法。在多个年龄段积累的临床经验表明，使用个体化最大耐受剂量（MTD）将获得羟脲治疗的最佳效果。然而，目前的经验和试错法剂量递增方法通常导致漫长的滴定过程，并且在许多诊所并没有严格执行。存在机会通过基于药代动力学模型的精准羟脲给药来快速实现个体 MTD。本综述旨在介绍定量建模方法的使用，包括贝叶斯自适应控制策略，用于精准羟脲给药。讨论了实施该方法的基本原理和实际考虑因素。还讨论了未来的研究方向，重点是将特定的安全性和其他临床结局终点纳入剂量选择决策中。
