环磷酰胺 (Cy) 是一种前药，主要由细胞色素 P450 (CYP) 2B6 酶生物激活。其他几种酶也参与其生物激活并影响其动力学。先前的研究已经表明酶的遗传多态性对 Cy 动力学及其临床结果的影响。这些结果存在争议，主要是因为 Cy 代谢途径中涉及几种相互作用的酶，这也可能受到多种临床因素以及其他药物相互作用的影响。在这篇综述文章中，我们介绍了 CYP2B6 多态性对 Cy 动力学的影响，因为它是主要的生物活化酶，并讨论了所有先前报道的可以改变 Cy 功效的酶和临床因素。此外，我们还解释了与其生物激活的性质和位点相关的关键 Cy 副作用。最后，我们讨论白消安在 Cy 代谢途径调理方案中的作用，作为涉及多种酶的药物间相互作用的临床实例。在本文结束时，我们的目标是提供 Cy 药物基因组学及其对其动力学的影响的全面总结。这些发现在开发 Cy 个性化患者剂量调整新策略中的应用将有助于未来优化患者特定 Cy 剂量，并最终改善临床结果。总之，CYP2B6 和其他几种酶多态性可以改变 Cy 动力学，从而改变临床结果。然而，任何个体患者的 Cy 动力学的精确量化都很复杂，因为它显然受到多因素遗传控制。此外，还应考虑其他临床因素，例如患者的年龄、诊断、合并用药和临床状态。版权所有 © 2024 Ibrahim El-Serafi 和 Sinclair Steele。

Cyclophosphamide (Cy) is a prodrug that is mainly bioactivated by cytochrome P450 (CYP) 2B6 enzyme. Several other enzymes are also involved in its bioactivation and affect its kinetics. Previous studies have shown the effect of the enzymes' genetic polymorphisms on Cy kinetics and its clinical outcome. These results were controversial primarily because of the involvement of several interacting enzymes in the Cy metabolic pathway, which can also be affected by several clinical factors as well as other drug interactions. In this review article, we present the effect of CYP2B6 polymorphisms on Cy kinetics since it is the main bioactivating enzyme, as well as discussing all previously reported enzymes and clinical factors that can alter Cy efficacy. Additionally, we present explanations for key Cy side effects related to the nature and site of its bioactivation. Finally, we discuss the role of busulphan in conditioning regimens in the Cy metabolic pathway as a clinical example of drug-drug interactions involving several enzymes. By the end of this article, our aim is to have provided a comprehensive summary of Cy pharmacogenomics and the effect on its kinetics. The utility of these findings in the development of new strategies for Cy personalized patient dose adjustment will aid in the future optimization of patient specific Cy dosages and ultimately in improving clinical outcomes. In conclusion, CYP2B6 and several other enzyme polymorphisms can alter Cy kinetics and consequently the clinical outcomes. However, the precise quantification of Cy kinetics in any individual patient is complex as it is clearly under multifactorial genetic control. Additionally, other clinical factors such as the patient's age, diagnosis, concomitant medications, and clinical status should also be considered.Copyright © 2024 Ibrahim El-Serafi and Sinclair Steele.