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Other Antiepileptic Drugs (other + antiepileptic_drug)
Selected AbstractsEffects of Valproate on Acylcarnitines in Children with Epilepsy Using ESI-MS/MSEPILEPSIA, Issue 1 2007Tamara Werner Summary:,Purpose: To determine the influence of valproate (VPA) treatment on acylcarnitines in children with epilepsy. Methods: Determination of acylcarnitines (including free carnitine and acylcarnitines from C2 to C18) in dried blood spot specimens using tandem-mass spectrometry. Longitudinal study of changes in acylcarnitines in children under VPA treatment without pretreatment (group 1) or with pretreatment with other antiepileptic drugs (group 2) before the start of VPA treatment at an early and a late treatment interval (12,66, 90,260 days after the beginning of treatment, respectively). Cross-sectional comparison of these two VPA groups and of a group receiving carbamazepine monotherapy (group 3) with controls. Results: Acylcarnitines in epileptic patients before VPA therapy did not differ from control values. In group 1, decreases of C0 (,26%), C2 (,12%), C16 (,31%), C18 (,41%), Ctotal (,10%), increases of C5OH (+31%), C8 (+33%) in the early treatment interval, and decreases of C16 (,21%), C18 (,42%), and increases of C2 (+26%), C5OH (+44%) in the late treatment interval were significant. In group 2, both in the longitudinal and the cross-sectional study, only a decrease of C18 (,41%, ,43%, respectively) in the late treatment interval was found. In group 3, no significant changes have been observed. Conclusions: We could prove changes in acylcarnitine subspecies, which were associated with VPA treatment in children with epilepsy. The treatment interval with the most marked changes coincides with the interval of highest risk for VPA-induced hepatotoxicity. The observed specific acylcarnitine pattern might point to the impaired intermediary metabolism that is responsible for VPA-induced hepatotoxicity. [source] Levetiracetam in the Treatment of Idiopathic Generalized EpilepsiesEPILEPSIA, Issue 2005Richard Grünewald Summary:, Since its introduction into clinical practice in 1999, levetiracetam, the S enantiomer of piracetam, has rapidly found a secure place, initially in the therapy of partial onset seizures and subsequently in the treatment of idiopathic generalized epilepsies (IGE). It has many of the properties of an "ideal" antiepileptic drug, including rapid absorption, linear pharmokinetics, and sparse drug interactions. Tolerabiliy is generally excellent in both adults and children, although tiredness is a common dose-limiting adverse effect. Occasionally the drug can precipitate behavioral abnormalities, especially in patients with learning disability. There is a wide safety margin in overdose. In common with most antiepileptic drugs its mode of action remains uncertain. Levetiracetam binds to a specific site in the brain, influences intracellular calcium currents and reverses negative allosteric modulators of GABA- and glycine-gated currents in vitro. Its effectiveness has been demonstrated in animal models of epilepsy and in clinical trials of partial onset and IGE. Treatment of IGEs may be straightforward, with many patients demonstrating an excellent and robust response to valproate monotherapy. However, there remains a significant minority of patients for whom valproate is unsuitable, including those who experience unacceptable adverse effects (e.g., weight gain or hair loss) and women of childbearing age in whom the teratogenic potential of valproate is unacceptable. Therapeutic response to lamotrigine in this group is often disappointing, and many clinicians now are turning to the choice of levetiracetam. Efficacy in generalized tonic,clonic seizures and myoclonus is usually apparent and some patients experience improvement in typical absences. Experience of combinations of levetiracetam with other antiepileptic drugs is limited in IGE and the responses are largely anecdotal. In our hands, patients with refractory IGEs may respond to combinations of levetiracetam with valproate, lamotrigine, and phenobarbital, and adverse effects when they occur are usually limited to tiredness. Levetiracetam does not interact with the oral contraceptive pill, simplifying treatment in women of childbearing age. Although animal data look encouraging, questions over levetiracetam's teratogenic potential and overall safety in pregnancy will remain for many years to come. [source] Pregabalin Drug Interaction Studies: Lack of Effect on the Pharmacokinetics of Carbamazepine, Phenytoin, Lamotrigine, and Valproate in Patients with Partial EpilepsyEPILEPSIA, Issue 9 2005Martin J. Brodie Summary:,Purpose: Pregabalin (PGB) is an ,2 -, ligand with demonstrated efficacy in epilepsy, neuropathic pain, and anxiety disorders. PGB is highly efficacious as adjunctive therapy in patients with refractory partial seizures. Methods: Given its efficacy as adjunctive therapy, the potential for interaction of PGB with other antiepileptic drugs (AEDs) was assessed in patients with partial epilepsy in open-label, multiple-dose studies. Patients received PGB, 600 mg/day (200 mg q8h) for 7 days, in combination with their individualized maintenance monotherapy with valproate (VPA), phenytoin (PHT), lamotrigine (LTG), or carbamazepine (CBZ). Results: Trough steady-state concentrations of CBZ (and its epoxide metabolite), PHT, LTG, and VPA were unaffected by concomitant PGB administration. Likewise, PGB steady-state pharmacokinetic parameter values were similar among patients receiving CBZ, PHT, LTG, or VPA and, in general, were similar to those observed historically in healthy subjects receiving PGB alone. The PGB,AED combinations were generally well tolerated. PGB may be added to VPA, LTG, PHT, or CBZ therapy without concern for pharmacokinetic drug,drug interactions. [source] Topiramate Enhances the Risk of Valproate-associated Side Effects in Three ChildrenEPILEPSIA, Issue 4 2002Elke Longin Summary: ,Purpose: We present three children with severe therapy-refractory epilepsy who tolerated valproate (VPA) well in various combinations with other antiepileptic drugs (AEDs) but developed typical VPA side effects in combination with topiramate (TPM). Methods: The clinical symptoms began with apathy in all three children; two of them also had hypothermia. Furthermore all children had elevated blood ammonia levels, one child in combination with increased liver transaminases and one with thrombocytopenia. Results: All children recovered completely after discontinuation of VPA or TPM. Conclusions: TPM seems likely to enhance the risk of side effects usually attributed to VPA and not described in TPM monotherapy. Our case reports suggest that possible adverse effects of VPA should be given particular attention when VPA is combined with TPM. [source] Chronological Changes of Plasma Homovanillic Acid (HVA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) Levels in 4 Patients with Temporal Lobe Epilepsy who Developed Psychosis-Like Symptoms (Hallucination and Delusion) During Zonisamide (ZNS) Administration.EPILEPSIA, Issue 2000Takuya Ueno Purpose: Zonisamide (ZNS) is a relatively new antiepileptic drug with an extensive therapeutic spectrum. However, ZNS can produce psychiatric side effects. In this study, we serially measured plasma hoinovaniliic acid (HVA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) levels in 4 patients with epilepsy who developed psychosis-like symptoms (hallucinations and delusions) during ZNS administration. Methods: Subjects comprised 4 patients (3 males and 1 female) with temporal lobe epilepsy ranging in age from 18 to 28 years. Intervals from the start of ZNS administration to the appearance of psychiatric symptoms ranged from 36 to 707 days. Intervals from achievement of the maximal dose to the appearance of psychiatric symptoms ranged from 2 to 240 days. In these 4 patients, the maximal doses of ZNS ranged from 300 to 600 mg/day. In 3 cases, serum ZNS levels were within the effective therapeutic concentration range wlicn syinptoms appeared. However, in 1 case, the serum ZNS level exceeded thc therapeutic level. In all cases, psychiatric symptoms disappeared after ZNS was switched to other antiepileptic drugs and anti-psychotic agents (2-5 mg/day of haloperidol or 10 mg/day of thioridazine) were added. In these cases, we serially measured plasma HVA and MHPG concentrations. Results: Case 1 was a 28-year-old male. Delusions of persecution appeared 190 days after ZNS administration was started. HVA levels at the appearance of psychiatric symptoms were 12.7 ng/ml and HVA levels at the disappearance of psychiatric symptoms were 7.4 ng/ml. MHPG levels at the appearance of psychiatric symptoms were 14.5 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 6. I ng/ml. When psychiatric symptoms appeared, the plasma HVA level was increased, whereas the MHPG level was slightly increased. Case 2 was an 18-year-old female. Auditory hallucinations appeared 320 days after ZNS first was administered. HVA levels at the appearance of psychiatric symptoms were 9.6- 10.0 nghl and HVA levels at the disappearance of psychiatric symptoms were 5.3,6.1 ng/ml. MHPG levcls at the appearance of psychiatric symptoms were 4.14.2 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 3.1 ng/ml. When psychiatric symptoms appeared, the plasma HVA level was increased, but there was no increase in MHPG. Case 3 was an 18-year-old male. Delusion of persecution appeared 707 days after ZNS administration was started. HVA levels at the appearance of psychiatric symptoms were 10.6 ng/ml and HVA levels at the disappearance of psychiatric symptoms were 7.2 ngiml. MHPG levels at the appearance of psychiatric symptoms were 5.3 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 3.9 ng/ml. When psychiatric symptoms appeared, plasma HVA level was increased, while the MHPG level was slightly increased. Case 4 was a 20-year-old male. Auditory hallucination appeared 36 days after ZNS was administered. HVA levels at the appearance of psychiatric symptoms were 13.6 ng/ml and HVA levels at the disappearance of psychiatric symptoms were 7.2 ng/ml. MHPG levels at the appearance of psychiatric symptoms were 5.4 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 6. I ng/ml. When psychiatric symptoms appeared, the plasma HVA level was increased, but there was no increase in MHPG. Conclusions: In all patients, the plasma HVA levels at the appearance of psychiatric symptoms was higher than the corresponding level at time of disappearance of psychiatric symptoms. Psychiatric symptoms may have been associated with activation of dopaniine by ZNS. MHPG levels were slightly increased in 2 cases. However, in thc other 2 cases, there were no changes in MHPG. The influence of ZNS on neurotransmitter metabolites should be further investigated in a larger nuniber of patients. [source] Lamotrigine pharmacokinetic/pharmacodynamic modelling in ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2005M.M. Castel-Branco Abstract The aim of this study was to perform a pharmacokinetic/pharmacodynamic (PK/PD) modelling of lamotrigine following its acute administration to rats. Adult male Wistar rats were given 10 mg/kg of lamotrigine intraperitoneally. Plasma and brain samples were obtained at predetermined times over 120 h post-dose and analysed by liquid chromatography. The anticonvulsant profile against maximal electroshock seizure stimulation was determined over 48 h after dosing. As a linear relationship between lamotrigine plasma and brain profiles was observed, only the plasma data set was used to establish the PK/PD relationship. To fit the effect,time course of lamotrigine, the PK/PD simultaneous fitting link model was used: the pharmacokinetic parameters and dosing information were used in the one-compartment first-order model to predict concentrations, which were then used to model the pharmacodynamic data with the sigmoid Emax model, in order to estimate all the parameters simultaneously. The following parameters were obtained: Vd = 2.00 L/kg, kabs = 8.50 h,1, kel = 0.025 h,1, ke0 = 3.75 h,1, Emax = 100.0% (fixed), EC50 = 3.44 mg/L and , = 8.64. From these results, it can be stated that lamotrigine is extensively distributed through the body, its plasma elimination half-life is around 28 h and a lamotrigine plasma concentration of 3.44 mg/L is enough to protect 50% of the animals. When compared with humans, the plasma concentrations achieved with this dose were within the therapeutic concentration range that had been proposed for epileptic patients. With the present PK/PD modelling it was possible to fit simultaneously the time-courses of the plasma levels and the anticonvulsant effect of lamotrigine, providing information not only about the pharmacokinetics of lamotrigine in the rat but also about its anticonvulsant response over time. As this approach can be easily applied to other drugs, it becomes a useful tool for an explanatory comparison between lamotrigine and other antiepileptic drugs. [source] Valproate-induced Parkinsonism in epilepsy patientsMOVEMENT DISORDERS, Issue 1 2007Dominic Jamora MD Abstract We systematically examined 226 epilepsy patients in a tertiary-referral center and found 6 (5.04%) to have valproate-induced Parkinsonism. There was a significantly higher prevalence of patients with Parkinsonism in the group of patients treated with valproate compared to those who were on other antiepileptic drugs (6 [5.04%] of 119 vs. 0 [0%] of 107; ,2 = 5.54; P = 0.025). These six patients had been on valproate for more than 3 years (mean, 75.67 ± 25.32 months) at an average dose of 750 ± 273.86 mg/day. The valproate doses were decreased or discontinued with supplementation from another antiepileptic medication. The mean UPDRS motor score significantly improved from 10.67 ± 5.1 to 4.75 ± 2.75 (P < 0.05). There was no relapse of seizures. Clinicians working in tertiary-referral centers should have a high index of suspicion for valproate-induced Parkinsonism. Early recognition and switching into another antiepileptic medication may help reduce unnecessary suffering in these patients. © 2006 Movement Disorder Society [source] | ||||||||||