Han Seunghoon, Na Gun Hyung, Kim Dong-Goo
Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul, South Korea.
Pharmacometrics Institute for Practical Education and Training, The Catholic University of Korea, Seocho-gu, Seoul, South Korea.
Drug Des Devel Ther. 2017 Jul 11;11:2099-2107. doi: 10.2147/DDDT.S134711. eCollection 2017.
Although individualized dosage regimens for anti-hepatitis B immunoglobulin (HBIG) therapy have been suggested, the pharmacokinetic profile and factors influencing the basis for individualization have not been sufficiently assessed. We sought to evaluate the pharmacokinetic characteristics of anti-HBIG quantitatively during the first 6 months after liver transplantation.
Identical doses of 10,000 IU HBIG were administered to adult liver transplant recipients daily during the first week, weekly thereafter until 28 postoperative days, and monthly thereafter. Blood samples were obtained at days 1, 7, 28, 84, and 168 after transplantation. Plasma HBIG titer was quantified using 4 different immunoassay methods. The titer determined by each analytical method was used for mixed-effect modeling, and the most precise results were chosen. Simulations were performed to predict the plausible immunoglobulin maintenance dose.
HBIG was eliminated from the body most rapidly in the immediate post-transplant period, and the elimination rate gradually decreased thereafter. In the early post-transplant period, patients with higher DNA titer tend to have lower plasma HBIG concentrations. The maintenance doses required to attain targets in 90%, 95%, and 99% of patients were ~15.3, 18.2, and 25.1 IU, respectively, multiplied by the target trough level (in IU/L).
The variability (explained and unexplained) in HBIG pharmacokinetics was relatively larger in the early post-transplant period. Dose individualization based upon patient characteristics should be adjusted focusing quantitatively on the early post-transplant period.
尽管已有人提出抗乙型肝炎免疫球蛋白（HBIG）治疗的个体化给药方案，但尚未充分评估其药代动力学特征及影响个体化的因素。我们试图评估肝移植术后前6个月内抗HBIG的药代动力学特征。
成年肝移植受者在术后第一周每天给予相同剂量的10,000 IU HBIG，此后每周给药直至术后28天，之后每月给药。在移植后第1、7、28、84和168天采集血样。使用4种不同的免疫测定方法对血浆HBIG滴度进行定量。将每种分析方法测定的滴度用于混合效应建模，并选择最精确的结果。进行模拟以预测合理的免疫球蛋白维持剂量。
移植后即刻HBIG从体内消除最快，此后消除率逐渐降低。在移植后早期，DNA滴度较高的患者血浆HBIG浓度往往较低。在90%、95%和99%的患者中达到目标所需的维持剂量分别约为15.3、18.2和25.1 IU，乘以目标谷浓度（单位为IU/L）。
移植后早期HBIG药代动力学的变异性（包括可解释和不可解释的）相对较大。基于患者特征的剂量个体化应重点在移植后早期进行定量调整。
