Maschio Marta, Albani Fiorenzo, Jandolo Bruno, Zarabla Alessia, Contin Manuela, Dinapoli Loredana, Fabi Alessandra, Pace Andrea, Baruzzi Agostino
Center for tumor-related epilepsy, Department of Neuroscience and Cervical-Facial Pathology, National Institute for Cancer "Regina Elena", Via Elio Chianesi 53, 00144 Rome, Italy.
J Neurooncol. 2008 Nov;90(2):217-21. doi: 10.1007/s11060-008-9651-0. Epub 2008 Jul 9.
Medical management of brain tumor-related epilepsy is complicated by interactions between antiepileptic and chemotherapeutic drugs. We studied the effect of temozolomide therapy on the disposition of the new antiepileptic drugs topiramate (TPM) or oxcarbazepine (OXC).
Fifteen patients chronically treated with TPM or OXC in monotherapy starting a chemotherapeutic treatment with temozolomide were enrolled in the study, of which ten were available for the final analyses. Blood samples were collected before temozolomide treatment (T(0)), at its end (T(7)) and after further 1-3 weeks (T(14)-T(28)). For each patient, more than one treatment cycle was studied. Topiramate and OXC mono-10-hydroxy derivative (MHD) plasma concentrations were determined by hplc coupled with ion spray mass spectrometer (TPM) or ultraviolet (MHD) detection.
Mean TPM concentrations were 5.4 +/- 2.4 microg/ml at T(0) vs. 5.5 +/- 2.4 microg/ml at T(7) (n = 14), and 5.4 +/- 2.4 microg/ml at T(0) vs. 5.6 +/- 2.8 microg/ml at T(14)-T(28) (n = 14). Mean MHD concentrations were 16.4 +/- 7.6 microg at T(0) vs. 18.5 +/- 9.0 microg/ml at T(7) (n = 5), and 16.8 +/- 7.0 microg/ml at T(0) vs. 18.0 +/- 8.7 microg/ml at T(14)-T(28) (n = 8) (all comparisons not statistically significant; Student's t-test for paired samples).
Temozolomide treatment did not affect TPM plasma concentrations in chronically treated patients. Data for MHD in OXC-treated patients were similar, but, due to the small sample size, results should be interpreted cautiously.These findings confirm that TPM (and possibly OXC) are a reasonable choice of antiepileptic drug in patients with brain tumor-related epilepsy.
脑肿瘤相关性癫痫的药物治疗因抗癫痫药物与化疗药物之间的相互作用而变得复杂。我们研究了替莫唑胺治疗对新型抗癫痫药物托吡酯（TPM）或奥卡西平（OXC）处置的影响。
15例长期接受TPM或OXC单药治疗并开始接受替莫唑胺化疗的患者纳入本研究，其中10例可用于最终分析。在替莫唑胺治疗前（T(0)）、治疗结束时（T(7)）以及进一步1 - 3周后（T(14) - T(28)）采集血样。对每位患者研究了不止一个治疗周期。采用高效液相色谱联用离子喷雾质谱仪（TPM）或紫外检测（MHD）测定托吡酯和奥卡西平单 - 10 - 羟基衍生物（MHD）的血浆浓度。
TPM的平均浓度在T(0)时为5.4±2.4μg/ml，T(7)时为5.5±2.4μg/ml（n = 14），T(0)时为5.4±2.4μg/ml，T(14) - T(28)时为5.6±2.8μg/ml（n = 14）。MHD的平均浓度在T(0)时为16.4±7.6μg/ml，T(7)时为18.5±9.0μg/ml（n = 5），T(0)时为16.8±7.0μg/ml，T(14) - T(28)时为18.0±8.7μg/ml（n = 8）（所有比较均无统计学意义；配对样本的学生t检验）。
替莫唑胺治疗对长期治疗患者的TPM血浆浓度无影响。奥卡西平治疗患者中MHD的数据相似，但由于样本量小，结果应谨慎解释。这些发现证实TPM（可能还有奥卡西平）是脑肿瘤相关性癫痫患者抗癫痫药物的合理选择。
