抗人T细胞猪免疫球蛋白治疗重型再生障碍性贫血患者的药物代谢动力学研究

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.