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目的观察和研究静脉滴注吉西他滨在老年非小细胞肺癌(nonsmall-cell lung cancer,NSCLC)患者体内的药动学参数变化规律,为合理制定化疗方案提供依据。方法选取30例无法进行手术切除治疗的老年NSCLC患者作为研究对象,对其应用静脉滴注1 000 mg/m2固定剂量的吉西他滨进行化疗,对给药后第10、30、50、60、75、90和120 min时患者的血药浓度和峰值血药浓度(Cmax)进行检测,并估算曲线下面积(area under the curve,AUC)、表观分布容积(Vd)、生物半衰期(t1/2)和总消除率(Cl)等药代动力学参数。结果静脉滴注应用吉西他滨的主要药动学参数为:t1/2为8.8~20.5 min,AUC为7.7~10.8μg/ml,Cl为2 600~3 450 ml/min,Cmax为10.7~18.3μg/ml,Vd为60~180 L,而在代谢产物中,t1/2为5.3~15.0 h,AUC为70.0~109.0μg/ml,Cl为48~156 ml/min,Cmax为22.6~29.5μg/ml,Vd为50~150 L。结论吉西他滨是老年晚期NSCLC化疗中常用的药物,具有确切的临床疗效,静脉应用时其药代动力学参数具有一定规律性,临床医生应根据其药代动力学参数制定合理的化疗方案,以达到降低毒性、提高临床收益的目的。
Objective To observe and study the regularity of pharmacokinetic parameters of intravenous gemcitabine in elderly patients with nonsmall-cell lung cancer (NSCLC), and to provide a basis for rational formulation of chemotherapy regimen. Methods Thirty elderly NSCLC patients who were unable to undergo surgical resection were enrolled in this study. Gemcitabine, a fixed dose of 1 000 mg / m 2, was given intravenously to patients with NSCLC at the 10th, 30th, The plasma concentration and peak plasma concentration (Cmax) were measured at 90 and 120 min, and the area under the curve (AUC), apparent volume of distribution (Vd) and biological half-life (t1 / 2) And total elimination rate (Cl) and other pharmacokinetic parameters. Results The main pharmacokinetic parameters of intravenous gemcitabine were as follows: t1 / 2 was 8.8-20.5 min, AUC was 7.7-10.8 μg / ml, Cl was 2.600-3.450 ml / min, Cmax was 10.7-18.3 μg / ml and Vd of 60-180 L, whereas in the metabolites, t1 / 2 is 5.3-15.0 h, AUC is 70.0-109.0 μg / ml, Cl is 48-156 ml / min, Cmax is 22.6-29.5 μg / ml , Vd is 50 to 150 L. Conclusion Gemcitabine is a commonly used drug in chemotherapy for advanced NSCLC in elderly patients with definite clinical efficacy. Pharmacokinetic parameters of intravenous injection of gemcitabine are of certain regularity. Clinicians should formulate rational chemotherapy regimens according to their pharmacokinetic parameters to achieve Reduce toxicity, improve clinical benefits.