鲁索利替尼
骨髓纤维化
医学
药代动力学
Janus激酶抑制剂
内科学
人口
真性红细胞增多症
分配量
原发性血小板增多症
胃肠病学
临床研究阶段
髓外造血
肿瘤科
贾纳斯激酶
骨髓
毒性
受体
环境卫生
造血
生物
遗传学
干细胞
作者
Xuejun Chen,William V. Williams,Victor Sandor,Swamy Yeleswaram
摘要
Ruxolitinib is a selective inhibitor of Janus kinase 1 and 2, which is approved to treat intermediate or high-risk myelofibrosis. The population pharmacokinetics for ruxolitinib were characterized by a modeling dataset of 272 subjects from a Phase 2 and a Phase 3 study and validated by an external validation dataset of 142 subjects from a second Phase 3 study. The PK of ruxolitinib was adequately described by a two-compartment disposition model with first-order absorption and linear elimination. All model parameters were estimated with good precision. Gender and body weight were identified as covariates for oral clearance (CL/F) and volume of distribution for central compartment (Vc/F), respectively. Apparent oral clearance was 22.1 and 17.7 L/h for a typical male and female subject, respectively, with 39.1% unexplained inter-individual variability (IIV). The typical Vc /F for a subject with a median weight of 72.9 kg was estimated to be 58.6 L, with 28% unexplained IIV. The model predictive performance was validated by visual predictive check (VPC) and the external validation dataset. This analysis suggests that effects of gender and body weight on ruxolitinib PK are not clinically significant and hence no dose adjustment is needed based on gender and weight.
科研通智能强力驱动
Strongly Powered by AbleSci AI