Effect of phenytoin on celecoxib pharmacokinetics in patients with glioblastoma
Effect of phenytoin on celecoxib pharmacokinetics in patients with glioblastoma
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DOI：
10.1215/15228517-2007-055
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发表时间：
2008-04-01
期刊：
影响因子：
15.9
通讯作者：
Supko, Jeffrey G.
中科院分区：
文献类型：
--
作者：
Grossman, Stuart A.;Olson, Jeffrey;Supko, Jeffrey G.
环氧合酶-2 （COX-2）的表达与许多恶性肿瘤的预后、血管生成和放射敏感性有关。塞来昔布是一种选择性COX-2抑制剂，主要通过肝脏代谢消除。本研究旨在探讨肝酶诱导抗癫痫药物（EIASDs）对塞来昔布药动学的影响。同时还评估了塞来昔布联合放疗治疗胶质母细胞瘤的安全性以及联合治疗对生存的影响。患者根据是否同时使用eiasd进行分层。塞来昔布（400）mg，每日口服两次，直至肿瘤进展或出现剂量限制性毒性。给予标准放疗，不进行辅助化疗。进行采样以确定塞来昔布初始剂量和稳态谷浓度的血浆浓度/时间分布。纳入35例患者（+EIASD 22例，-EIASD 13例）。两组患者在年龄、运动状态、手术程度或迷你精神状态测试得分方面无显著差异。这种治疗耐受性良好。+ElASD组所有患者均服用苯妥英。15例+EIASD和12例-EIASD患者的塞来昔布药动学参数均无显著差异。35例患者中有31例死亡，所有患者的估计中位生存时间为12个月（+EIASD， 11.5个月；-EIASD， 16个月；p = 0.11）。塞来昔布的药代动力学不受同时施用苯妥英的显著影响。在放疗期间和放疗后给予塞来昔布耐受性良好。+EIASD组和-EIASD组之间的潜在生存差异值得进一步评估。
Cyclooxygenase-2 (COX-2) expression has been linked to the prognosis, angiogenesis, and radiation sensitivity of many malignancies. Celecoxib, a selective COX-2 inhibitor, is predominantly eliminated by hepatic metabolism. This study was conducted to determine the effects of hepatic enzyme-inducing antiseizure drugs (EIASDs) on the pharmacokinetics of celecoxib. The safety of celecoxib administered with radiation for glioblastoma and the effect of the combined treatment on survival were also evaluated. Patients were stratified based on concomitant use of EIASDs. Celecoxib (400) mg was administered orally twice a day until tumor progression or dose-limiting toxicity. Standard radiation was administered without adjuvant chemotherapy. Sampling was performed to define the plasma concentration/time profile for the initial dose of celecoxib and steady-state trough concentrations. Thirty-five patients (22 +EIASD, 13 -EIASD) were enrolled. There were no significant differences in age, performance status, extent of surgery, or Mini Mental State Exam scores between the two cohorts. The treatment was well tolerated. All patients in the +ElASD arm were taking phenytoin. There were no significant differences in any celecoxib pharmacokinetic parameters between 15 +EIASD and 12 -EIASD patients. With 31 of 35 patients deceased, estimated median survival time for all patients was 12 months (+EIASD, 11.5 months; -EIASD, 16 months; p = 0.11). The pharmacokinetics of celecoxib is not significantly affected by the concomitant administration of phenytoin. Celecoxib administered during and after radiation is well tolerated. The potential difference in survival between the +EIASD and -EIASD groups deserves further evaluation.