期刊
CLINICAL PHARMACOLOGY & THERAPEUTICS
卷 86, 期 2, 页码 190-196出版社
WILEY
DOI: 10.1038/clpt.2009.80
关键词
-
资金
- US Food and Drug Administration Orphan Product [FD0003498-01]
- Clinical Translational Study Award [1UL1RR024156]
In a pralatrexate phase I study, patients displayed a high incidence of mucositis of grades 3 and 4. Preliminary evaluations of the pharmacokinetics of the drug and its association with mucositis suggested that pralatrexate exposure (area under the concentration-time curve (AUC)) could be controlled with body size (e. g., weight or body surface area)-based dosing and that pretreatment with folic acid and vitamin B-12 might diminish the incidence and severity of mucositis. The study was amended, with revised dosing and vitamin B-12 administration. Data from 47 patients were evaluated using NONMEM. Weight and methylmalonic acid (MMA) level were predictive of pharmacokinetic (PK) variability. AUC and MMA level were positively correlated with the risk of developing mucositis. A lower AUC schedule with vitamin B-12 pretreatment may control mucositis without compromising efficacy. The covariates identified in this study are comparable with other antifolate analogs. The application of modeling was a critical step in the development of pralatrexate, yielding important suggestions for dose, scheduling, and pretreatment modifications.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据