Background: Cyclophosphamide (CP) is an anticancer alkylating group (nitrogen mustard) and a prodrug that will be metabolized to form its active metabolite, 4-hydroxycyclophosphamide (4-OHCP). The various enzymes involved in its bioactivation can cause a wide range of CP expression and activity among patients and ultimately affect the metabolism, efficacy and toxicity of this drug. The effectiveness of CP therapy can be determined by 4-OHCP level in dried blood spot (DBS).
Aim: The purpose of this study was to conduct the phenotyping of CP 4-hydroxylation rate in Malay cancer patients.
Methodology: Phenotyping study of CP 4-hydroxylation rate to 40 subjects of Malay cancer patients was done based on the value of its bioactivity ratio (4-OHCP to CP levels).
Results: The result shown the cyclophosphamide 4-hydroxylation rate of 80% (n=32) subjects as ultrarapid metabolizer (UM) and 20% (n=8) as poor metabolizer (PM).
Conclusion: Phenotyping study of CP 4-hydroxylation in Malay cancer patients can be conducted by quantifying CP bioactivity ratio (4-OHCP to CP level) in dried blood spot. In majority of Malay cancer patients, cyclophosphamide would be bioactivated through 4-hydroxylation in hepar rapidly as indicated by the high value of the bioactivity ratio or the increased CP clearance and 4-OHCP level.



中文翻译：

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环磷酰胺4-羟基化在马来癌症患者中的表型研究

背景：环磷酰胺 (CP) 是一种抗癌烷基化基团（氮芥）和前药，可被代谢形成其活性代谢物 4-羟基环磷酰胺 (4-OHCP)。参与其生物活化的各种酶可在患者中引起广泛的CP表达和活性，最终影响该药物的代谢、疗效和毒性。CP 治疗的有效性可以通过干血斑 (DBS) 中的 4-OHCP 水平来确定。
目的：本研究的目的是对马来癌症患者的 CP 4-羟基化率进行表型分析。
方法：根据其生物活性比值（4-OHCP 与 CP 水平）对 40 名马来癌症患者的 CP 4-羟基化率进行表型研究。
结果：结果显示，80% (n=32) 受试者的环磷酰胺 4-羟基化率为超快代谢者 (UM)，20% (n=8) 受试者为慢代谢者 (PM)。
结论：可以通过量化干血斑中 CP 的生物活性比（4-OHCP 与 CP 水平）来进行马来癌症患者 CP 4-羟基化的表型研究。在大多数马来癌症患者中，环磷酰胺会通过肝中的 4-羟基化迅速被生物活化，这表明其生物活性比值较高或 CP 清除率和 4-OHCP 水平增加。