抗胸腺细胞球蛋白在HLA配型部分相合造血干细胞移植患者药代.docVIP

抗胸腺细胞球蛋白在HLA配型部分相合造血干细胞移植患者药代 　【摘要】 为了研究抗胸腺细胞球蛋白（antithymocyte globulin, ATG）在HLA配型部分相合造血干细胞移植患者体内的药代动力学，将2003年10月至2004年10月北京大学血液病研究所骨髓移植部15例患者纳入本研究方案并应用ATG，其中AML 5例、CML 6 例、ALL 3例、AA 1例。给15例接受HLA部分配型相合造血干细胞移植术患者静脉滴注ATG，剂量为10 mg/kg,分4天给药，用 ELISA Fc法检测ATG血药浓度，用3P97程序根据房室模型进行数据处理。结果表明： ATG为超长半衰期药物,剂量2.5 mg/d连续应用4天，血药浓度随之升高，移植前5天血药浓度上升到44.8%。根据AIC(Akaike’s information criterion)，该值符合一级消除动力学的二室模型；主要药代动力学参数： AUC0t 3 415.9 ±216.2 mg/（L·d） ; Cmax 136.0±10.31 mg/L， ATG的达峰时间（Tmax）为4.8±0.7天； t1/2 为29. 7±2.60天； ATG表观分布容积的平均值为 0.12±0.02 L/kg； CL(s) 为0.002927 L/d， ATG体内有效的血药浓度至少维持90天。在给药期间患者未出现严重药物不良反应，耐受性好。结论： 含总剂量10 mg ATG预处理方案，临床有效，患者安全耐受，适宜用于HLA部分相合的造血干细胞移植患者，ATG在机体的药代动力学无种族差异性。 【关键词】 抗胸腺细胞球蛋白 药代动力学 HLA配型部分相合造血干细胞移植 Pharmacokinetics of Antithymocyte Globulin in Recipients Undergoing HLA Partially matched Hematopoietic Stem Cell Transplantation Abstract The aim of study was to investigate the pharmacokinetics and distribution of antithymocyte globulin(ATG) in recipients of partially HLAmatched hematopoietic stem cell transplantation. Fifteen patients with hematological disorders were received hematopoietic stem cell transplantation from partially HLAmatched related donor between October 2003 and October 2004 in the Institute of Hematology and People Hospital, Peking University. All patients including 5 cases of AML, 6 cases of CML, 3 cases of ALL, 1 case of AA were consecutively enrolled in the present study after providing written informed consent. Antithymocyte globulin was administered before allogeneic hematopoietic stem cell transplantation at a dose of 2.5 mg/kg daily for 4 consecutive days (total dose of 10 mg/kg) in the conditioning regimen. The concentration of rabbit ATG in the serum of 15 patients was measured using a new enzymelinked immunoabsorbent assay (ELISA) for the Fc portion of rabbit IgG. The results showed that the washout phase of ATG elimination was analyzed over 0-120 days, results were wellfitted by a single exponential decay giving a mean el