Temozolomide treatment does not affect topiramate and oxcarbazepine plasma concentrations in chronically treated patients with brain tumor-related epilepsy |
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Authors: | Marta Maschio Fiorenzo Albani Bruno Jandolo Alessia Zarabla Manuela Contin Loredana Dinapoli Alessandra Fabi Andrea Pace Agostino Baruzzi |
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Institution: | (1) 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;(2) Laboratory of Clinical Neuropharmacology, Department of Neurological Sciences, University of Bologna, Via Ugo Foscolo 7, 40123 Bologna, Italy;(3) Division of Clinical Oncology, National Institute for Cancer “Regina Elena”, Via Elio Chianesi 53, 00144 Rome, Italy;(4) Department of Neuroscience and Cervical-Facial Pathology, National Institute for Cancer “Regina Elena”, Via Elio Chianesi 53, 00144 Rome, Italy |
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Abstract: | Objective 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). Methods 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 (T0), at its end (T7) and after further 1–3 weeks (T14–T28). 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. Results Mean TPM concentrations were 5.4 ± 2.4 μg/ml at T0
vs. 5.5 ± 2.4 μg/ml at T7 (n = 14), and 5.4 ± 2.4 μg/ml at T0
vs. 5.6 ± 2.8 μg/ml at T14–T28 (n = 14). Mean MHD concentrations were 16.4 ± 7.6 μg at T0
vs. 18.5 ± 9.0 μg/ml at T7 (n = 5), and 16.8 ± 7.0 μg/ml at T0
vs. 18.0 ± 8.7 μg/ml at T14–T28 (n = 8) (all comparisons not statistically significant; Student’s t-test for paired samples). Conclusion 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. |
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Keywords: | Drug interactions Oxcarbazepine Temozolomide Topiramate Brain tumor-related epilepsy |
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