Objective: To study the metabolic characteristics of anti-human T-cell porcine immunoglobulin (p-ATG) in patients with severe aplastic anemia (SAA) . Methods: For patients with SAA treated with p-ATG combined cyclosporine A (CsA) immunosuppressants between February 2017 and December 2017, the p-ATG dose was 20 mg·kg(-1)·d(-1) over 12 h of intravenous administration for 5 consecutive days. The blood concentration of p-ATG was detected by the three-antibody sandwich ELISA method, the pharmacokinetic analysis software was fitted, and the second-chamber model method was used to calculate the pharmacokinetic parameters and plot the pharmacokinetic curve. Adverse events were recorded and the hematologic reactions were determined at 6 months after treatment. Results: Sixteen patients with SAA treated with p-ATG were enrolled, including 8 females and 8 males, with a median age of 22 years (range, 12 to 49 years) and a median weight of 62.5 kg (range, 37.5 to 82.0 kg) . The pharmacokinetics of p-ATG could be evaluated in 14 cases. p-ATG is distributed in vivo as a two-chamber model, with an average drug concentration peak (T(max)) of (5.786±2.486) days, a peak concentration (C(max)) of (616±452) mg/L, and a half-life of (10.479±8.242) days. The area under the drug time curve (AUC) was (5.807±3.236) mg/L·d. Six months after treatment, 8 of 14 patients received a hematologic response; the AUC (0-t) of the effective group and ineffective groups was (7.50±3.26) mg/L·d vs (4.50±2.18) mg/L·d, and the C(max) was (627±476) mg/L vs (584±382) mg/L, respectively. Conclusion: The plasma concentration of p-ATG reached a peak after 5 days of continuous infusion, and then decreased slowly, with a half-life of 10.479 days, and the residual drug concentration was detected in the body 60 days after administration. A relationship between drug metabolism and efficacy and adverse reactions could not be determined.
目的： 研究抗人T细胞猪免疫球蛋白（p-ATG）在重型再生障碍性贫血（SAA）患者的药物代谢特点。 方法： 2017年2月至2017年12月纳入接受p-ATG联合环孢素A（CsA）免疫抑制治疗的SAA患者，p-ATG剂量为20 mg·kg(-1)·d(-1)，持续12 h静脉给药，连续5 d。应用三抗体夹心ELISA方法检测p-ATG血药浓度，药代动力学分析软件拟合，计算相关参数并绘制药物代谢曲线。随访记录不良事件并评估治疗后6个月血液学反应。 结果： 入组16例接受p-ATG治疗的SAA患者，女8例，男8例，中位年龄22（12~49）岁，中位体重62.5（37.5~82.0）kg。其中14例可进行p-ATG药代动力学评价。p-ATG在体内分布为二室模型，平均药物浓度峰值时间（T(max)）为（5.786±2.486）d，平均峰浓度（C(max)）为（616±452）mg/L，平均半衰期（T(1/2)）为（10.479±8.242）d。平均药物浓度时间曲线下面积[AUC(（0-t）)]为（5.807±3.236）mg/L·d。14例患者治疗后6个月8例获得血液学反应，有效组与无效组患者AUC(（0-t）)分别为（7.50±3.26）mg/L·d对（4.50±2.18）mg/L·d，C(max)分别为（627±476）mg/L对（584±382）mg/L。 结论： 连续5 d输注后p-ATG血药浓度达峰值，后缓慢下降，半衰期10.479 d，用药后60 d体内检测到残存药物浓度。尚不能得出药物代谢与疗效及不良反应的关系。.
Keywords: Anemia, aplastic; Antithymocyte globulin; Pharmacokinetics.