5－Fu的药代动力学研究及其在化疗中的合理应用

应用高效液相色谱法测定血药浓度,对８例滋养细胞肿瘤患者静脉滴注５－氟尿嘧啶（５－Ｆｕ）的药代动力学进行了研究。结果表明,５－Ｆｕ在体内衰减呈二室开放模型。主要药代动力学参数：ｔ１／２α为１．８３３８±０．６７３６ｍｉｎ,ｔ１／２β为２４．４５８±８．５３２２ｍｉｎ,Ｖ１为１４．６９４１±１０．９９２７Ｌ,ＣＬ为３．５８１９±２．４０８８１／ｍｉｎ,ＡＵＣ为６００．５６３６±３７７．６４２１μｇ／ｍｉｎ·ｍｌ－１。３例化疗过程中出现骨髓抑制的患者其消除半衰期较无毒性反应患者明显延长（Ｐ＜０．０５）。作者认为（１）虽然抗肿瘤药物的疗效已得到公认,但仍应强调在滋养细胞肿瘤以及其他恶性肿瘤治疗中应合理应用化疗。（２）为使化疗更为有效、安全,医院应建立治疗药物监测系统。

Study on the pharmacokinetics of 5-Fu and its rational chemotherapy for patients with trophoblastic tumors

The pharmacokinetics of 5-fluorouracil(5-Fu) was studied in 8 patients with trophoblastic tumors who received intravenous infusion of 5-Fu. 5-Fu concentrations were measured in these patients' sera by high performance liquid chromatography (HPLC).Serum concentrations of 5-Fu confirmed to a two-compartment open model adequately. The pharmacokinetic parameters were found to be: 1. 8338min, 24 . 458,V1: 14.6941/L, CL: 3.5819L/min and AUC: 600.5636 (μg.min) /ml.Clinical toxicities occoured following 5-Fu courses were observed in three patients who suffered from myelosuppression and had a markedly prolonged 5-Fu .Based on these data as well as the review of related literatures,the authors proposed: 1 ,The rational use of chemotherapy in cases with malignant trophoblastic tumors,even in all cases with malignant tumors, should be emphasized,although the effectiveness of those cancerocidal drugs are well known by most clinicians. 2, The "therapeutic drug monitoring" should be established as a constant system in all hospitals, where the cheniotherapy are used mostly, in order to make sure both the effect of drugs used and the safty of patients treated.