卡培他滨代谢产物 5'-脱氧-5-氟胞苷的代谢转化与肌酐清除率的相关性。
Correlation Between the Metabolic Conversion of a Capecitabine Metabolite, 5'-Deoxy-5-fluorocytidine, and Creatinine Clearance.
机构信息
Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan
Department of Breast and Endocrine Surgery, Nagoya University Hospital, Nagoya, Japan.
出版信息
In Vivo. 2020 Nov-Dec;34(6):3539-3544. doi: 10.21873/invivo.12196.
AIM
Capecitabine is a prodrug that is metabolized to its active form, 5-fluorouracil (5-FU), in three enzymatic steps. This prospective pharmacokinetic study evaluated cytidine deaminase (CDA) activity, the second drug-metabolizing enzyme that generates 5'-deoxy-5-fluorouridine (5'-DFUR) from 5'-deoxy-5-fluorocytidine (5'-DFCR), as well as creatinine clearance (CLcr).
PATIENTS AND METHODS
Patients with colorectal cancer who received capecitabine plus oxaliplatin were selected. Pharmacokinetics of capecitabine and its metabolites, and CDA activity in plasma were analyzed.
RESULTS
Eighteen patients were examined. The area under the plasma concentration-time curve (AUC) of 5'-DFUR showed a significant inverse correlation with CLcr (p=0.003). The metabolic ratio, i.e. the ratios of the AUC of 5'-DFUR plus that of 5-FU to the AUC of 5'-DFCR, significantly increased when CLcr decreased (p=0.001) but did not depend on plasma CDA activity.
CONCLUSION
Metabolism of 5'-DFCR to form 5'-DFUR increased as CLcr decreased but the mechanism remains unknown.
目的
卡培他滨是一种前体药物，可在三个酶促步骤中代谢为其活性形式 5-氟尿嘧啶（5-FU）。本前瞻性药代动力学研究评估了胞苷脱氨酶（CDA）活性，该酶是将 5'-脱氧-5-氟胞苷（5'-DFCR）生成 5'-去氧-5-氟尿苷（5'-DFUR）的第二种药物代谢酶，以及肌酐清除率（CLcr）。
患者和方法
选择接受卡培他滨联合奥沙利铂治疗的结直肠癌患者。分析了卡培他滨及其代谢物的药代动力学以及血浆中的 CDA 活性。
结果
检查了 18 名患者。5'-DFUR 的血浆浓度-时间曲线下面积（AUC）与 CLcr 呈显著负相关（p=0.003）。代谢比，即 AUC5'-DFUR 加 AUC5-FU 与 AUC5'-DFCR 的比值，当 CLcr 降低时显著增加（p=0.001），但与血浆 CDA 活性无关。
结论
随着 CLcr 的降低，5'-DFCR 代谢为 5'-DFUR 的增加，但机制尚不清楚。
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