Saleh Mohammad I, Melhim Suhad Bani, Al-Ramadhani Hanguin M, Alzubiedi Sameh
School of Pharmacy, The University of Jordan, Amman, 11942, Jordan.
Eur J Drug Metab Pharmacokinet. 2019 Feb;44(1):31-42. doi: 10.1007/s13318-018-0490-x.
Eltrombopag is a thrombopoietic growth factor that is approved for the treatment of thrombocytopenia in chronic hepatitis C virus (HCV) patients. We aimed to describe eltrombopag population pharmacokinetics in hepatitis C patients. Bayesian statistical approach will be applied to screen for patients' characteristics associated with eltrombopag pharmacokinetic parameters.
A population pharmacokinetic analysis was conducted using WinBUGS version 1.4.3. Data from 483 individuals with chronic HCV infection were analyzed. This analysis is a secondary analysis of two clinical studies (ENABLE1 and ENABLE2) sponsored by GlaxoSmithKline. Several patients' characteristics were examined as possible covariates of the population pharmacokinetic model. Prior information from previous studies was incorporated in the bayesian model as prior distribution to estimate pharmacokinetic parameters.
A two-compartment pharmacokinetic model with first-order absorption with exponential error model best fit the data. We identified East Asian race and total bilirubin level as predictors of eltrombopag clearance. Typical value for distributional clearance was 0.762 L/h (95% Bayesian credible set, 0.703-0.826), for volume of distribution of the central and peripheral compartments were 12 L (10.9-13.4) and 10.9 L (10.4-11.5), and for absorption lag time was 0.947 h (0.918-0.977). Assuming an average total bilirubin of 21.7 µmol/L, the typical elimination clearance value for an East Asian patient was 0.14 L/h and for other races was 0.20 L/h.
Eltrombopag pharmacokinetic behavior was described using population bayesian approach. This model can be applied to optimize eltrombopag dosing in order to reduce the incidence of thrombocytopenia in HCV-infected patient receiving interferon-based therapy.
艾曲泊帕是一种血小板生成生长因子，已被批准用于治疗慢性丙型肝炎病毒（HCV）患者的血小板减少症。我们旨在描述丙型肝炎患者中艾曲泊帕的群体药代动力学。将应用贝叶斯统计方法筛选与艾曲泊帕药代动力学参数相关的患者特征。
使用WinBUGS 1.4.3版进行群体药代动力学分析。分析了483例慢性HCV感染个体的数据。该分析是对葛兰素史克赞助的两项临床研究（ENABLE1和ENABLE2）的二次分析。检查了几个患者特征作为群体药代动力学模型的可能协变量。将先前研究的先验信息作为先验分布纳入贝叶斯模型以估计药代动力学参数。
具有一级吸收和指数误差模型的二室药代动力学模型最适合数据。我们确定东亚种族和总胆红素水平为艾曲泊帕清除率的预测因素。分布清除率的典型值为0.762 L/h（95%贝叶斯可信区间，0.703 - 0.826），中央和外周室的分布容积分别为12 L（10.9 - 13.4）和10.9 L（10.4 - 11.5），吸收滞后时间为0.947 h（0.918 - 0.977）。假设平均总胆红素为21.7 µmol/L，东亚患者的典型消除清除率值为0.14 L/h，其他种族为0.20 L/h。
使用群体贝叶斯方法描述了艾曲泊帕的药代动力学行为。该模型可用于优化艾曲泊帕给药，以降低接受基于干扰素治疗的HCV感染患者血小板减少症的发生率。
