已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

Population Pharmacokinetics of Ruxolitinib in Patients with aGVHD Who Had an Inadequate Response to Corticosteroids

鲁索利替尼 医学 骨髓纤维化 人口 内科学 队列 骨髓 环境卫生
作者
Xuejun Chen,Xiang Liu,Phillip Wang,Swamy Yeleswaram
出处
期刊:Blood [Elsevier BV]
卷期号:134 (Supplement_1): 4534-4534 被引量:2
标识
DOI:10.1182/blood-2019-124027
摘要

Background: Jakafi® (ruxolitinib) is currently approved for the treatment of adult patients with intermediate- and high-risk myelofibrosis (MF) and for the treatment of adult patients with polycythemia vera (PV) who have had an inadequate response to or are intolerant to hydroxyurea. A prospective, open-label, single-cohort, Phase 2 study (REACH1) was conducted to evaluate the safety and efficacy of Jakafi® (ruxolitinib) in patients with acute graft versus host disease (aGVHD) who have had an inadequate response to corticosteroids. A population PK analysis was employed to characterize the PK of ruxolitinib in this patient population. Patients and Methods: REACH1, Study INCB 18424-251, and COMFORT-I are the 3 studies supporting the population PK of ruxolitinib; the first study is in participants with aGVHD who have had an inadequate response to corticosteroids, and the other 2 studies are in participants with MF. First, the final PK model for ruxolitinib in patients with MF was applied to the data in patients with MF and aGVHD. When significant biases were observed in this validation process, new population PK models were developed based on the pooled data. The accuracy and robustness of the final population PK model were assessed using a predictive check method. Results: An under-prediction bias was observed at the population level when existing PK model in MF was applied to pooled data in patients with MF and aGVHD. A new model was developed to account for the under prediction bias at the population level. The final population PK model for ruxolitinib was a 2 compartment disposition model with first order absorption, absorption lag time, and linear elimination. Body weight and gender were significant predictors of the volume of distribution of the central compartment and oral clearance, respectively. Patients with aGVHD showed lower oral clearance (66.7%) and slower rate of absorption (~28%) than that in patients with MF. The stage of liver involvement in GVHD and use of moderate or potent CYP3A4 inhibitors were identified as covariates for ruxolitinib CL. Conclusion: The population PK analysis supports the proposed dose regimen in patients with aGVHD who had an inadequate response to corticosteroids as well as dose recommendations for DDI and subjects with organ dysfunction. Disclosures Chen: Incyte Research Institute: Employment. Liu:Incyte Research Institute: Employment. Wang:Incyte Research Institute: Employment. Yeleswaram:Incyte Research Institute: Employment.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
刚刚
猪猪hero应助科研通管家采纳,获得10
3秒前
猪猪hero应助科研通管家采纳,获得10
3秒前
烟花应助科研通管家采纳,获得10
3秒前
丘比特应助科研通管家采纳,获得30
3秒前
coolkid应助科研通管家采纳,获得10
3秒前
Ava应助科研通管家采纳,获得10
3秒前
5秒前
5秒前
尊敬代亦完成签到,获得积分10
6秒前
xiaomeng完成签到 ,获得积分10
7秒前
马尔斯完成签到,获得积分10
7秒前
8秒前
13秒前
carl完成签到,获得积分10
13秒前
负责怀莲发布了新的文献求助10
16秒前
nidejun完成签到,获得积分10
16秒前
Lucas应助Sophia采纳,获得10
17秒前
19秒前
nidejun发布了新的文献求助10
21秒前
21秒前
mit完成签到 ,获得积分10
21秒前
momo发布了新的文献求助10
23秒前
yexu845发布了新的文献求助10
24秒前
26秒前
康阿蛋发布了新的文献求助10
26秒前
lu完成签到,获得积分10
29秒前
30秒前
研友_VZG7GZ应助yexu845采纳,获得10
30秒前
儒雅致远发布了新的文献求助10
31秒前
32秒前
涛1118完成签到,获得积分10
34秒前
35秒前
阿卡波糖拌饭完成签到,获得积分20
37秒前
涛1118发布了新的文献求助10
39秒前
39秒前
40秒前
44秒前
45秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989857
求助须知:如何正确求助?哪些是违规求助? 3531994
关于积分的说明 11255679
捐赠科研通 3270758
什么是DOI,文献DOI怎么找? 1805053
邀请新用户注册赠送积分活动 882195
科研通“疑难数据库(出版商)”最低求助积分说明 809208