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Enzyme-inducing Antiepileptic Drugs (enzyme-inducing + antiepileptic_drug)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Hyperhomocysteinemia in epileptic patients on new antiepileptic drugs

EPILEPSIA, Issue 2 2010
Vincenzo Belcastro
Summary Purpose:, Older enzyme-inducing antiepileptic drugs (AEDs) may induce supraphysiologic plasma concentrations of total (t) homocysteine (Hcy). The aim of the present study was to investigate the effect of new AEDs on plasma tHcy levels. Methods:, Patients 18,50 years of age, on AEDs monotherapy, with no other known cause of hyper-tHcy were enrolled. Plasma tHcy, folate, vitamin B12, and AEDs levels were determined by standard high-performance liquid chromatography (HPLC) methods. Methylenetetrahydrofolate-reductase (MTHFR) polymorphisms were checked using Puregene genomic DNA purification system (Gentra, Celbio, Italy). A group of healthy volunteers matched for age and sex was taken as control. Results:, Two hundred fifty-nine patients (151 on newer and 108 on older AEDs) and 231 controls were enrolled. Plasma tHcy levels were significantly higher [mean values, standard error (SE) 16.8, 0.4 vs. 9.1, 0.2 ,m; physiologic range 5,13 ,m] and folate lower (6.3, 0.1 vs. 9.3, 0.1 nm; normal > 6.8 nm) in patients compared to controls. Patients treated with oxcarbazepine, topiramate, carbamazepine, and phenobarbital exhibited mean plasma tHcy levels above the physiologic range [mean values (SE) 16 (0.8), 19.1 (0.8), 20.5 (1.0), and 18.5 (1.5) ,m, respectively]. Conversely, normal tHcy concentrations were observed in the lamotrigine and levetiracetam groups [both 11.1 (0.5) ,m]. Discussion:, Oxcarbazepine and topiramate might cause hyper-tHcy, most likely because of the capacity of these agents to induce the hepatic enzymes. Because literature data suggest that hyper-tHcy may contribute to the development of cerebrovascular diseases and brain atrophy, a supplement of folate can be considered in these patients to normalize plasma tHcy. [source]

Vitamin D Levels and Bone Turnover in Epilepsy Patients Taking Carbamazepine or Oxcarbazepine

EPILEPSIA, Issue 3 2006
Scott Mintzer
Summary:,Purpose: Evidence suggests that enzyme-inducing antiepileptic drugs (AEDs) may decrease serum 25-hydroxyvitamin D (25-OHD) levels and increase bone turnover. We sought to determine whether these are affected by treatment with carbamazepine (CBZ) or oxcarbazepine (OXC). Methods: We measured serum levels of 25-OHD, parathyroid hormone (PTH), osteocalcin (OCLN), bone alkaline phosphatase (BAP), and urinary N-telopeptides of type I collagen cross-links (NTX) in normal controls (n = 24) and in epilepsy patients taking CBZ (n = 21) or OXC (n = 24) in monotherapy. CBZ patients were subsequently switched overnight to OXC monotherapy, and after 6 weeks, the tests were repeated. Results: 25-OHD levels were lower in each drug-treated group (OXC, 19.4 ± 2.3 pg/ml; CBZ, 20.4 ± 2.4) than in the controls (27.5 ± 2.8) (ANOVA, p = 0.052). This difference was significant for the OXC group (p < 0.05). PTH, BAP, and NTX did not differ significantly among groups. OCLN levels were somewhat elevated in the OXC group (2.79 ± 0.47 ng/ml) and more clearly and significantly elevated in the CBZ group (3.63 ± 0.36) compared with controls (2.38 ± 0.41) (p = 0.053). Because the data were very similar between OXC and CBZ groups, they were combined to increase statistical power. The combined drug-treatment group had significantly higher BAP (p = 0.02) and lower 25-OHD (p = 0.015) than did controls. The latter remained significant even after accounting for the confounding effects of age on 25-OHD levels (p < 0.05). No significant differences were found after CBZ patients were switched to OXC. Conclusions: Epilepsy patients taking OXC or CBZ have significantly lower 25-OHD than do normal controls, with a pattern of changes in other bone biomarkers suggestive of secondary hyperparathyroidism. It may be prudent for patients taking CBZ or OXC to be prescribed 25-OHD replacement. [source]

Oxcarbazepine treatment in male epilepsy patients improves pre-existing sexual dysfunction

ACTA NEUROLOGICA SCANDINAVICA, Issue 2 2009
G. Luef
Objective,,, To collect data on sexual dysfunction in a larger population of male patients with epilepsy treated with oxcarbazepine in a naturalistic setting. Patients and methods,,, Six hundred seventy-three adult male patients with partial epilepsy in whom monotherapy with oxcarbazepine was indicated were evaluated at baseline and after approximately 12 weeks of treatment with regard to the number of seizures and occurrence of any adverse drug reactions. All patients were questioned regarding their sexual function. Results,,, Out of 228 patients with pre-existing sexual function impairment at baseline, an improvement was observed in 181 (79.4%) patients, 23 (10.1%) patients experienced no impairment at the final visit. The improvements were more marked in those patients, who were pretreated with enzyme-inducing antiepileptic drugs. No worsening of the sexual dysfunction was observed. Conclusions,,, Oxcarbazepine was found to have beneficial effects on sexual dysfunction and to be effective and well tolerated in male patients with partial epilepsy. [source]

Phase I pharmacokinetic study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor vatalanib (PTK787) plus imatinib and hydroxyurea for malignant glioma

CANCER, Issue 10 2009
David A. Reardon MD
Abstract BACKGROUND: This study determined the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of the oral vascular endothelial growth factor receptor (VEGFR) inhibitor, vatalanib, when administered with imatinib and hydroxyurea on a continuous daily schedule among recurrent malignant glioma patients. METHODS: All patients received 500 mg of hydroxyurea twice daily. Imatinib was dosed at 400 mg per day for patients not taking enzyme-inducing antiepileptic drugs (EIAEDs; stratum A) and at 500 mg twice-a-day for patients taking EIAEDs (stratum B). Vatalanib was escalated from 500 mg to 1250 mg twice daily in successive cohorts, independently for each stratum. Pharmacokinetics of each drug were assessed. RESULTS: A total of 37 recurrent patients, 34 (92%) with glioblastoma and 3 (8%) with grade 3 malignant glioma, were enrolled. Nineteen patients (51%) were taking EIAEDs. The MTD of vatalanib for all patients was 1000 mg twice-a-day. DLTs were hematologic, gastrointestinal, renal, and hepatic. No patients developed intracranial hemorrhage. Concurrent administration of imatinib and hydroxyurea did not affect vatalanib exposure, but EIAEDs decreased vatalanib and imatinib plasma exposures. CONCLUSIONS: Vatalanib doses up to 1000 mg twice-a-day combined with imatinib and hydroxyurea were well tolerated. Strategies to target tumor blood vessel endothelial cells and pericytes by inhibiting VEGFR and platelet-derived growth factor, respectively, were safe among recurrent malignant glioma patients and may enhance antiangiogenesis activity. Cancer 2009. © 2009 American Cancer Society. [source]