Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new trileptal research articles will be listed here shortly after becoming available to us.
Related Sponsors
Medical research on trileptal
Curr Treat Options Neurol. 2008 Jul; 10(4): 260-8
Shaw SJ, Krauss GL
Generic antiepileptic drugs (AEDs) generally provide safe, effective, lower-cost alternatives to brand-name drugs. To be approved by the US Food and Drug Administration (FDA), manufacturers must show that generic drugs are comparable to brand-name formulations, meeting bioequivalence, dissolution, and manufacturing quality standards. Bioequivalence for most generic formulations is evaluated by measuring blood pharmacokinetic values in a small, crossover study of adult volunteers taking single doses of brand-name and generic AEDs. Bioequivalence standards require that ratios of average peak drug concentrations (C(max)) and total extent of absorption (area under the curve, AUC) for a test drug be within 80% to 125% of the reference brand-name drug, with a confidence interval of 90%. Bioequivalence of most generic AEDs, however, has not been evaluated in patients with epilepsy or in other special populations such as elderly patients or patients taking multiple AEDs and prodrugs. Moreover, evidence is limited regarding the adequacy of FDA generic standards for AEDs, particularly for "narrow therapeutic ratio" medications such as oxcarbazepine, although two carbamazepine studies are supportive. Most patients can successfully initiate therapy with generic AEDs and can safely switch from brand-name to generic AEDs (and sometimes back again). The FDA, however, has not shown safety in generic-to-generic switches, which could potentially cause drug concentration changes of up to 40%. Less expensive generic formulations will soon be available for most of the "second generation" AEDs--onisamide, for example, recently had 17 generic formulations approved in the United States--providing substantial savings in health care costs. In summary, although generic AEDs are generally safe and effective for most patients, the current bioequivalence standards may not be sufficient for certain patient populations and for certain drugs, requiring vulnerable patients to be monitored very carefully when converting to generic AEDs. The adequacy or inadequacy of FDA bioequivalence standards for AEDs has not yet been well evaluated with large, well-controlled studies.
[The use of the antiepileptic drug trileptal in the clinical practice.]
Zh Nevrol Psikhiatr Im S S Korsakova. 2008; 108(5): 47-50
Gromov SA, Eroshina ES, Lipatova LV
The data on therapeutical efficacy of the new antiepileptic drug trileptal (oxcarbazepine) and results of the own observations of 38 patients with partial epilepsy who received trileptal as mono- or polytherapy are presented. The high efficacy and good tolerability of the drug has been shown. The seizure control has been obtained in 84% of patients.
Chemotherapy-induced peripheral neuropathy: Prevention and treatment strategies.
Eur J Cancer. 2008 Jun 18;
Wolf S, Barton D, Kottschade L, Grothey A, Loprinzi C
Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose limiting side effect of many commonly used chemotherapeutic agents, including platinum drugs, taxanes, epothilones and vinca alkaloids, and also newer agents such as bortezomib and lenolidamide. Symptom control studies have been conducted looking at ways to prevent or alleviate established CIPN. This manuscript provides a review of studies directed at both of these areas. New evidence strongly suggests that intravenous calcium and magnesium therapy can attenuate the development of oxaliplatin-induced CIPN, without reducing treatment response. Accumulating data suggest that vitamin E may also attenuate the development of CIPN, but more data regarding its efficacy and safety should be obtained prior to its general use in patients. Other agents that look promising in preliminary studies, but need substantiation, include glutamine, glutathione, N-acetylcysteine, oxcarbazepine, and xaliproden. Effective treatment of established CIPN, however, has yet to be found. Lastly, paclitaxel causes a unique acute pain syndrome which has been hypothesised to be caused by neurologic injury. No drugs, to date, have been proven to prevent this toxicity.
A study on epileptic negative myoclonus in atypical benign partial epilepsy of childhood.
Brain Dev. 2008 Jun 16;
Yang Z, Liu X, Qin J, Zhang Y, Bao X, Chang X, Wang S, Wu Y, Xiong H
Objective. To investigate the clinical and neurophysiological characteristics, particularly therapeutic considerations, of epileptic negative myoclonus (ENM) in atypical benign partial epilepsy (ABPE) of childhood. Methods. From 1998 to 2006, 14/242 patients with benign children epilepsy with centrotemporal spikes (BECTS) were diagnosed as having ABPE with ENM. In all 14 patients, we performed video-EEG monitoring along with tests with the patient's arms outstretched; 6/14 patients were also simultaneously underwent surface electromyogram (EMG). ENM manifestations, electrophysiological features, and responses to antiepileptic drugs were analyzed. Results. In all cases, ENM developed after the onset of epilepsy and during antiepileptic drug therapy, and the appearance of ENM were corresponding to EEG findings of high-amplitude spikes followed by a slow wave in the contralateral motor areas with secondary generalization. This was further confirmed by time-locked silent EMG. During ENM occurrence or recurrence, habitual seizures and interictal discharges were exaggerated. In some patients, the changes in antiepileptic drug regimens in relation to ENM appearance included add-on therapy with carbamazepine, oxcarbazepine, and phenobarbital or withdrawal of valproate. ENM was controlled in most cases by administration of various combinations of valproate, clonazepam, and corticosteroids. Conclusion. The incidence of ENM or ABPE in our center was approximately 5.79%. A combination of video-EEG monitoring with the patient's arms outstretched and EMG is essential to identify ENM. The aggravation of habitual seizures and interictal discharges indicate ENM. Some antiepileptic drugs, such as carbamazepine, oxcarbazepine, and phenobarbital, may be related to ENM occurrence during spontaneous aggravation of ABPE. Various combinations of valproate, benzodiazepines, and corticosteroids are relatively effective for treating ENM that occurs in ABPE.
Estimating the effects of co-medications on plasma olanzapine concentrations by using a mixed model.
Prog Neuropsychopharmacol Biol Psychiatry. 2008 May 7;
Botts S, Diaz FJ, Santoro V, Spina E, Muscatello MR, Cogollo M, Castro FE, de Leon J
The purpose of this study was to estimate the effect sizes of drug interactions on plasma olanzapine concentrations while adjusting for potentially confounding factors such as smoking. The estimation was performed by using a mixed model, data from a series of previously published studies of lamotrigine, oxcarbazepine, topiramate, and mirtazapine, and unpublished data from patients under clinical therapeutic drug monitoring (TDM). The total sample included 163 adult patients (age >/=18 years) who provided both steady-state plasma olanzapine concentrations and smoking information. They provided a total of 360 olanzapine concentrations (1 to 11 measures per patient). Smoking and concomitant carbamazepine or lamotrigine use were found to have significant effects on median plasma olanzapine concentrations. The effects of lamotrigine on plasma olanzapine concentrations were modified by smoking. After adjusting for olanzapine dose and carbamazepine intake, plasma olanzapine concentrations were 10% lower in non-smokers who were taking lamotrigine than in non-smokers who were not taking lamotrigine; olanzapine concentrations were 35% higher in smokers who were taking lamotrigine than in smokers who were not taking lamotrigine; olanzapine concentrations were 41% lower in smokers who were not taking lamotrigine than in non-smokers who were not taking lamotrigine; and olanzapine concentrations were 11% lower in smokers who were taking lamotrigine than in non-smokers who were taking lamotrigine. After adjusting for olanzapine dose and taking carbamazepine, the correction factor comparing smokers taking lamotrigine versus non-smokers who were not taking lamotrigine was 1.3. Gender, age, and concomitant use of mirtazapine, valproic acid, lamotrigine, topiramate, lorazepam, citalopram or oxcarbazepine did not have significant effects on olanzapine concentrations. The main limitation of this clinical design is the unavoidable substantial "noise" that characterizes (uncontrolled) clinical environments, which may make it difficult to detect the effects of some variables. Other limitations were the small sample size of some drug sub-samples and the lack of testing for plasma olanzapine metabolites.
J Clin Pharmacol. 2008 May 28;
Almeida L, Minciu I, Nunes T, Butoianu N, Falcão A, Magureanu SA, Soares-da-Silva P
This study investigates the pharmacokinetics of eslicarbazepine acetate (ESL), a new voltage-gated sodium channel blocker, in epileptic children aged 2 to 7 years (n = 11) and 7 to 11 years (n = 8) and adolescents aged 12 to 17 years (n = 10). The study explores ESL efficacy and tolerability. Patients were treated with ESL once-daily doses of 5 mg/kg/day on weeks 1 to 4, 15 mg/kg/day on weeks 5 to 8, and 30 mg/kg/day (or 1800 mg/day, whichever was less) on weeks 9 to 12. At the end of each 4-week period, a 24-hour pharmacokinetic profiling was performed. Similar to adults, ESL was rapidly metabolized to eslicarbazepine. In all age groups, eslicarbazepine peak concentrations were reached 0.5 hour to 3 hours after ESL dosing, and Cmax and AUC0-24 were dose proportional. Eslicarbazepine Cmax was similar between age groups following administration of identical ESL dose/kg, but AUC0-24 depended on age due to a faster plasma clearance of eslicarbazepine in younger children compared with adolescents. R-licarbazepine and oxcarbazepine were minor metabolites. A dose-dependent decrease in seizure frequency was observed in children aged 2 to 7 years and adolescents aged 12 to 17 years but not in children aged 7 to 11 years. One patient in each group became seizure free. ESL was generally well tolerated.
J Clin Psychiatry. 2008 Apr; 69(4): 676-8
Yeh YW, Wang TY, Huang CC, Chen YC
Generalized tonic-clonic seizures after acute oxcarbazepine withdrawal.
Neurology. 2008 May 27; 70(22 Pt 2): 2187-8
Azar NJ, Wright AT, Wang L, Song Y, Abou-Khalil BW
Trends in antiepileptic drug prescribing for older patients with new-onset epilepsy: 2000-2004.
Neurology. 2008 May 27; 70(22 Pt 2): 2171-8
Pugh MJ, Van Cott AC, Cramer JA, Knoefel JE, Amuan ME, Tabares J, Ramsay RE, Berlowitz DR,
BACKGROUND: Newer antiepileptic drugs (AEDs) have been shown to be equally efficacious as older seizure medications but with fewer neurotoxic and systemic side effects in the elderly. A growing body of clinical recommendations based on systematic literature review and expert opinion advocate the use of the newer agents and avoidance of phenobarbital and phenytoin. This study sought to determine if changes in practice occurred between 2000 and 2004--a time during which evidence and recommendations became increasingly available. METHODS: National data from the Veterans Health Administration (VA; inpatient, outpatient, pharmacy) from 1998 to 2004 and Medicare data (1999-2004) were used to identify patients 66 years and older with new-onset epilepsy. Initial AED was the first AED received from the VA. AEDs were categorized into four groups: phenobarbital, phenytoin, standard (carbamazepine, valproate), and new (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate). RESULTS: We found a small reduction in use of phenytoin (70.6% to 66.1%) and phenobarbital (3.2% to 1.9%). Use of new AEDs increased significantly from 12.9% to 19.8%, due primarily to use of lamotrigine, levetiracetam, and topiramate. CONCLUSIONS: Despite a growing list of clinical recommendations and guidelines, phenytoin was the most commonly used antiepileptic drug, and there was little change in its use for elderly patients over 5 years. Research further exploring physician and health care system factors associated with change (or lack thereof) will provide better insight into the impact of clinical recommendations on practice.
The antinociceptive effects of anticonvulsants in a mouse visceral pain model.
Anesth Analg. 2008 Jun; 106(6): 1897-903
Stepanovic-Petrovic RM, Tomic MA, Vuckovic SM, Paranos S, Ugresic ND, Prostran MS, Milovanovic S, Boskovic B
BACKGROUND: There is evidence supporting the antinociceptive effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in various models of neuropathic pain as well as inflammatory somatic pain. Data are lacking on the antinociceptive potential of these drugs against visceral pain. In this study, we examined and compared the effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in the writhing test as a visceral pain model in the mouse. In addition, the influence of these anticonvulsants on motor performance was examined to compare the tolerability of these anticonvulsants when used against acute visceral pain. METHODS: The antinociceptive effects of these anticonvulsants were examined in the acetic acid writhing test in mice. The side effect propensity of these drugs was examined using the rotarod test. RESULTS: Carbamazepine (25-60 mg/kg; p.o.), oxcarbazepine (10-40 mg/kg; p.o.), gabapentin (10-70 mg/kg; p.o.), and topiramate (5-30 mg/kg; p.o.) caused a significant dose-dependent reduction the number of writhes in the writhing test. In the rotarod test, carbamazepine (60-140 mg/kg; p.o.) and oxcarbazepine (120-450 mg/kg; p.o.) significantly reduced the time spent on the rotarod in a dose- and time-dependent manner. Gabapentin (1000-2000 mg/kg; p.o.) and topiramate (400-1500 mg/kg; p.o.) did not produce significant impairment of motor performance at the highest doses used. The therapeutic index (motor impairing dose TD(50)/writhing ED(50)) values were topiramate (>148.5) > gabapentin (>60.2) > oxcarbazepine (15.2) > carbamazepine (2.3). CONCLUSIONS: These results indicate that oxcarbazepine, gabapentin, and topiramate are effective in the writhing model in mice, in a dose range, which is not related to motor impairment; topiramate is the most potent and the most tolerable drug.