培美曲塞
医学
加药
药代动力学
血液透析
肾功能
人口
药理学
肺癌
肿瘤科
毒性
泌尿科
内科学
化疗
环境卫生
顺铂
作者
Nikki de Rouw,Sander Croes,Rein Posthuma,D.E. Agterhuis,Janna Schoenmaekers,Hieronymus J. Derijks,David M. Burger,A. Dingemans,Rob ter Heine
出处
期刊:Lung Cancer
[Elsevier]
日期:2019-04-01
卷期号:130: 156-158
被引量:9
标识
DOI:10.1016/j.lungcan.2019.01.018
摘要
Objectives Pemetrexed is indicated for non-small cell lung cancer and mesothelioma. Dosing is based on body surface are (BSA), while renal function is the only determinant for exposure and thus toxicity. BSA-based dosing introduces large variability in exposure and may lead to (hemato)toxicity in patients with impaired renal function. Therefore, pemetrexed is contraindicated in renal impairment. The presented cases provide proof-of-concept for pharmacokinetically-guided dosing of pemetrexed in a haemodialysis patient and a patient with mild renal impairment. Methods The pharmacokinetic target was an area under the concentration-time curve (AUC) of 123–205 mg·h/L. Using a previously developed population pharmacokinetic model, individual pharmacokinetics were estimated. Results Both patients had an exposure above target after the initial dose, but a proportional dose reduction resulted in a therapeutic exposure in both patients (185 and 166 mg·h/L, respectively), that was well-tolerated. Interestingly, a threefold increase in systemic clearance of pemetrexed was observed during hemodialysis (from 1.00 L/h to 3.01 L/h), which approximates the population clearance of pemetrexed. Conclusion Altogether, we showed that pharmacokinetically-guided dosing of pemetrexed may be a feasible strategy for patients with lung cancer and renal impairment.
科研通智能强力驱动
Strongly Powered by AbleSci AI