氟尿苷在滋养细胞肿瘤患者中的临床药动学研究

 目的研究氟尿苷在滋养细胞肿瘤患者体内的药动学特征。方法本实验对12名氟尿苷化疗患者进行了临床药动学研究，其中单药化疗6例，联合化疗6例。采用8 h恒速静脉输注的给药方式，分别于输注中及输注后50 min内动态采集血清标本，用HPLC测定血药浓度。采用Winnonlin程序进行模型数据拟合并计算药动学参数。结果氟尿苷在体内符合三室开放模型，单药化疗时具有非线性特征，在体内能够代谢为5FU。结论氟尿苷非线性代谢特征对临床应用具有重要意义。

Pharmacokinetics of floxuridine in patients with trophoblastic Tumors

OBJECTIVE To investigate the disposition of floxuridine in patients with trophoblastic tumors.METHODS 12 patients with trophoblastic tumors were divided into FUDR and FUDR+KSM group.FUDR was administered by an 8 hour infusion.The blood samples were obtained during the infusion and up to 50 min after the infusion.The concentrations of floxuridine in serum were measured by a reverse phase high performance liquid chromatography.The pharmacokinetics of floxuridine was assessed by noncompartment and compartment model.RESULTS The disposition of floxuridine was nonlinear,consistent with a three compartment model.The metabolite fluorouracil was found after iv administration of floxuridine.CONCLUSION Floxuridine was eliminated primarily by a dose dependent process.Such characteristics may be related to unexpected stronger pharmacological effects if increasing the dose or reducing the infusion time.