羟基喜树碱I期药代动力学及人体耐受性的临床研究

目的研究羟基喜树碱（HCPT）I期药代动力学及人体耐受性。方法：选取2014年8月-2015年8月期间在我院治疗的25例恶性肿瘤患者为研究对象，将其分为5组，每组5例患者。分别将5．0 mg／m2、7．5 mg／m2、12 mg／me、16 mg／m2、20 mg／m2剂量的羟基喜树碱（TCPT）溶于100 mL的O．9％NaCl溶液中，30 min内恒速静脉滴注，连续使用5 d，停药2周后观察患者临床反应，同时取2 mL给药第1天给药前、停药后即可、停药后15 min、30min、1 h、2 h、4 h、6 h、8h、12 h静脉血，将其分别置于肝素试管中，采用高效液相荧光法分别测定羟基喜树碱（HCPT）在人体的血药浓度。结果：25例患者均表现骨髓抑制、腹泻，并且患者不良反应发生率与强度呈线性增加，此外还伴随轻微的恶心、呕吐、血尿、皮疹以及肝功能异常。HCPT在人体内呈二室模型，tl／2a 0．052 4-0．061 4 h，t1/213 1．031—2．421 h，Vd 5．541—11．41 L／m2；临床患者最大的耐受剂量为16 mg／m2d，临床推荐剂量为12 mg／m2d。结论：HCPT在临床中主要的不良反应为消化道反应和骨髓抑制，并且随着剂量的增加反应加重，停药后可恢复正常。

Objective To study the hydroxy camptothecin （HCPT） I pharmacokinetic and human tolerance. Methods：selected during August 2014 to August 2015 in our hospital clinical data of 25 patients with malignant tumor treatment as theresearch object, it can be divided into 5 groups, each group of five patients. Respectively 5.0 mg/m2, 7.5 mg/m2, 12 mg/m2,16 mg/m2, 20 mg/m2 doses of hydroxy camptothecin （HCPT） dissolved in 100 ml of 0.9% NaC1 solution, constant speedintravenous drip within 30 minutes, use 5 days in a row, stopped the clinical reactions were observed after 2 weeks, and at thesame time take 2 mL for 1 day delivery before and after drug withdrawal, 15 min after the drug was stopped, 30 min, 1 h, 2 h,4 h, 6 h, 8 h, 12 h venous blood, it put in heparin in vitro, respectively were determined by high performance liquidfluorescence hydroxy camptothecin （HCPT） in human blood drug concentration. Results： 25 cases were bone marrowsuppression and diarrhea, and the incidence of adverse reactions in patients with and intensity increased linearly, and alsowith mild nausea, vomiting, blood in urine, skin rashes and abnormal liver function. HCPT in a 2 rooms in the human bodymodel, t1/2 a 0. 052 4-0.061 4 h, t 1/2 beta 1.031- 2.421 h, Vd 5.541-11.41 L/m2; Clinical patients with maximumtolerance dose of 16 mg/m2d, clinical recommended dose of 12 mg/m2d. Conclusion： HCPT in clinical main clinical adversereaction in the digestive tract and bone marrow suppression, and with the increase of the dose is aggravating, adverse reactionscan be stopped or symptomatic treatment.