Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Blood Cells Mol Dis. 2017 Sep;67:135-142. doi: 10.1016/j.bcmd.2017.08.009. Epub 2017 Aug 8.
Hydroxyurea is a potent disease-modifying therapeutic agent with efficacy for the treatment of sickle cell anemia. When administered at once-daily oral doses that lead to mild marrow suppression, hydroxyurea leads to substantial and sustained fetal hemoglobin induction, which effectively inhibits erythrocyte sickling. When escalated to maximum tolerated dose, hydroxyurea has proven laboratory and clinical effects for both children and adults with sickle cell anemia. However, there is substantial inter-patient variability with regard to the optimal dosing regimen, as well as differences in treatment-related toxicities and responses that may be explained by hydroxyurea pharmacokinetics and pharmacogenetics. Addressing the safety and efficacy of hydroxyurea treatment requires quantitative and accurate drug analysis, and various laboratory techniques have been established. We review the historical and current analytical techniques for measuring hydroxyurea concentrations accurately, and discuss clinical settings where quantitative analysis can increase understanding and safety of this important therapeutic agent, and ultimately improve patient outcomes.
羟脲是一种有效的治疗镰状细胞贫血的疾病修饰治疗药物。当以每日一次的口服剂量给药导致轻度骨髓抑制时，羟脲可导致大量和持续的胎儿血红蛋白诱导，从而有效地抑制红细胞镰变。当增加到最大耐受剂量时，羟脲已被证明对镰状细胞贫血的儿童和成人具有实验室和临床效果。然而，在最佳剂量方案方面存在很大的个体间变异性，以及与治疗相关的毒性和反应的差异，这可能可以通过羟脲的药代动力学和药物遗传学来解释。解决羟脲治疗的安全性和疗效需要定量和准确的药物分析，并且已经建立了各种实验室技术。我们回顾了历史上和当前的分析技术，以准确测量羟脲浓度，并讨论了定量分析可以增加对这种重要治疗药物的理解和安全性并最终改善患者结局的临床环境。
