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Solitary cysticercus granuloma - a benign form of parenchymal neurocysticercosis - is considered as the most common cause of partial seizures. This study comparatively evaluated the seizure-related prognosis in patients with new-onset seizure having solitary cysticercus granuloma and in patients with normal neuroimaging. We also assessed the factors of seizure recurrence.
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A case note survey of 100 outpatients with a clinical diagnosis of bipolar affective disorder in a UK inner city teaching hospital revealed monotherapy with a mood stabilizer in only 23% of patients, mostly lithium (15%). Overall, 51% of patients were prescribed lithium, 19% carbamazepine and 5% valproate with only 8% receiving a combination of two mood stabilizers. Treatment appeared to be inadequate in 13/51 of patients on lithium, 9/19 of those on carbamazepine and 1/5 of those on valproate. Antipsychotics were used as monotherapy in 20% of patients and combined with a mood stabilizer in 43% of patients. Only 6% of patients were on atypical antipsychotics. These findings suggest that the treatment for many patients does not match recommendations. Clearer evidence on the place of combination mood stabilizers and adjunctive antipsychotics, particularly atypicals is needed in the treatment of bipolar affective disorder.
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Twelve patients with facial neuralgias diagnosed and treated in dental clinic of the Lagos University Teaching Hospital were studies. Using strict for diagnosis, patients were categorized into: trigeminal, glosspharyngeal and post herpetic neuralgias.
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Successful therapy with valproate and carbamazepine in patients with psychiatric disorders led to investigation of other anticonvulsants for similar indications. Gabapentin is a relatively new anticonvulsant being investigated for potential use in the treatment of bipolar disorder (BD), anxiety disorders, behavioral dyscontrol, and substance use disorders. Its favorable side effect profile, absence of the need for therapeutic drug monitoring, and minimal drug interactions give gabapentin a potential role in these indications. Computer searches of the biomedical literature were undertaken to identify all pertinent case reports, case series, and studies of the drug as monotherapy or adjunctive therapy for BD; 10 reports were retrieved. In the treatment of various anxiety disorders, one study, one case report, and one case series were identified. At least one case series described gabapentin therapy for alcohol withdrawal and one case report of the drug for agitation associated with dementia. Published, well-designed studies evaluating the agent's effectiveness as monotherapy for BD are lacking. Its benefit as an adjunctive treatment with other mood stabilizers is also unestablished. Data regarding its efficacy in the treatment of anxiety disorders or manifestations of substance abuse are limited. These areas may deserve further investigation.
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To identify the major risk factors for the increased incidence of congenital malformations in offspring of mothers being treated for epilepsy with antiepileptic drugs (AEDs) during pregnancy and, to determine the relative teratogenic risk of AEDs, we prospectively analyzed 983 offspring born in Japan, Italy, and Canada. The incidence of congenital malformations in offspring without drug exposure was 3.1%, versus an incidence with drug exposure of 9.0%. The highest incidence in offspring exposed to a single AED occurred with primidone (PRM; 14.3%), which was followed by valproate (VPA; 11.1%), phenytoin (PHT; 9.1%), carbamazepine (CBZ; 5.7%), and phenobarbital (PB; 5.1%). The VPA dose and level positively correlated with the incidence of malformations. This study first determined a cut-off value of VPA dose and level at 1000 mg/day and 70 microg/ml, respectively, to avoid the occurrence of malformations. The incidence of malformations increases as the number of drugs increases, and as the total daily dose increases. Specific combinations of AEDs such as VPA + CBZ and PHT + PRM + PB produced a higher incidence of congenital malformations. The incidence of malformations was not associated with any background factors studied except for the presence of malformations in siblings. These results indicate that the increased incidence of congenital malformations was caused primarily by AEDs, suggesting that malformations can be prevented by improvements in drug regimen, and by avoiding polypharmacy and high levels of VPA (more than 70 microg/ml) in the treatment of epileptic women of childbearimg age.
We report a case with bipolar II disorder having mixed features, in which refractory insomnia persisted. We diagnosed his case as mixed depression with mood fluctuations because increased impulsivity and buying sprees became remarkable, with diminished ability to think or concentrate. Switching to carbamazepine and risperidone improved his mood fluctuations and impulsivity. Nevertheless, his intermittent awakening (fragmentation of the sleep-wake rhythm), related dysfunctional beliefs, anxiety about sleep, and mild impulsivity persisted. The addition of various benzodiazepine sleeping drugs, bromovalerylurea, and antipsychotics did not improve insomnia. His intractable insomnia was markedly responsive to gabapentin, engendering further improvement of mood symptoms. Eventually, its efficacy achieved his reinstatement at work. Results of this case suggest the clinical use of gabapentin for treating bipolar disorder, especially in cases with intractable insomnia, which is a very important point in the symptoms and therapeutics of bipolar disorder.
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Bipolar disorder is more common in family practice than previously believed. Drug treatments for this complex disorder have evolved rapidly over the past decade, radically changing its management. Treatment now tends to be very successful.
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Carbamazepine-specific CD4(+), CD8(+), and CD4(+)CD8(+) T cells exist in the peripheral circulation of hypersensitive patients, often many years after the resolution of clinical manifestations.
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The effect of lithium on second messengers as etiological factor in the evolution of psoriasis in this patient were discussed.
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This is a retrospective, observational study in a tertiary epilepsy centre. Overall, 584 patients were followed during a ten-year period. Kaplan-Meier survival analysis was used to estimate the cumulative probability of retention. Cox proportional hazard model was used to analyze the risk factors for retention rate.
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132 responded (22%): 81% were paediatricians and 95% at consultant seniority. We estimated, annually, 751 new RE cases and 233 PS cases. Electroencephalography (EEG) is requested at least half the time in approximately 70% of cases; MRI brain at least half the time in 40%-65% cases and neuropsychological evaluation in 7%-8%. Clinicians reported non-treatment in 40%: main reasons were low frequency of seizures and parent/child preferences. Carbamazepine is the preferred older, and levetiracetam the preferred newer, RCT arm. Approximately one-half considered active and placebo designs acceptable, choosing seizures as primary and cognitive/behavioural measures as secondary outcomes.
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A strong stimulus intensity (three-fold higher than after-discharge threshold) was used to elicit drug-resistant seizures in a rat amygdala kindling model. Vehicle, low-dose PER (0.75 mg/kg), or high-dose PER (1.5mg/kg), in combination with vehicle, levetiracetam (LEV) 50mg/kg, lamotrigine (LAM) 20mg/kg, carbamazepine (CBZ) 20mg/kg, or valproic acid (VPA) 200mg/kg, were administered intraperitoneally to groups of 6-13 rats. Seizure score, electroencephalography (EEG) seizure duration, and motor seizure duration were evaluated, with pharmacodynamic interactions determined by two-way analysis of variance (ANOVA). Motor impairment was evaluated by rotarod test and two-way ANOVA.
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The aim of this study was to evaluate the impact of polymorphisms in the EPHX1 (c.416A > G, c.337T > C) and CYP3A4*22 genes involved in carbamazepine (CBZ) metabolism and pharmacoresistance among 118 Tunisian patients with epilepsy under maintenance dose of CBZ. These genetic polymorphisms were analyzed by PCR-RFLP. Associations between plasma CBZ concentration, CBZ-E concentration, maintenance doses and metabolic ratio (CBZ-E:CBZ, CBZ-D:CBZ-E) were analyzed with each polymorphism. Both variants of EPHX1 c.416A > G and c.337T > C are significantly associated with higher metabolic ratio CBZ-E:CBZ and seem to decrease the activity of the epoxide hydrolase. The CYP3A4*22 variant allele is significantly associated with lower CBZ-D:CBZ-E ratio and seems also to be associated with less activity of the cytochrome. Our data suggest that certain polymorphisms of metabolizing enzyme genes could influence inter-individual variability of CBZ metabolism.
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The long-term course and the frequency of relapses for various peripheral vestibular disorders and somatoform phobic postural vertigo are discussed with respect to the clinically most important questions for thus afflicted patients. This review is mainly based on our own long-term follow-up studies and takes into consideration the most relevant literature. The following syndromes are discussed in detail. Vestibular neuritis: the recovery rate of peripheral vestibular function lies between 40-63% depending on early-onset treatment with corticosteroids; the recurrence rate within 10 years is 2%. Menière's disease} loss of auditory and vestibular function occurs mainly in the first 5 to 10 years; frequency of vertigo attacks may decline after 5 to 10 years; bilateral involvement increases with increasing duration of the condition in up to 30-50%; vestibular drop attacks may occur early or late within the course, mostly with spontaneous remission; high-dose and long-term treatment with betahistine significantly reduces attack frequency in Menière's disease, Benign paroxysmal positioning vertigo: the recurrence rate is 50% within 10 years (in females 58%, in males 39%), most recurrences (80%) being observed within the first year after initial relief; recurrence rate in the seventh decade is half of that in the sixth decade. Vestibular paroxysmia: medical treatment with carbamazepine or oxcarbazepine leads to a continuous significant reduction in attack frequency, intensity, and duration of 10-15% of baseline. Bilateral vestibulopathy: recovery of vestibular function is limited to single cases depending on their etiology. Phobic postural vertigo: within 5 to 16 years 27% of the patients are symptom-free, 48% improve, 22% remain unchanged, and 3% worsen; a detailed explanation of the mechanisms that cause and the factors that provoke attacks is imperative, as well as instructions for self-controlled desensitization within the context of behavioral therapy.
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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.
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In vivo fraction absorbed plots indicated that the three generic formulations were absorbed more rapidly than the innovator product, and the mean time of maximum plasma concentration was 6-7 hr sooner for the generic formulations. The mean maximum plasma concentration ranged from 17-19 percent higher for the generic products compared to the innovator, and the 90% confidence limits for Cmax data ranged from 11 1% to 126%. The mean AUC(0-infinity) for the generic products ranged from 101-104% compared to the innovator, and the confidence limits for AUC ranged from 97-108%.
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The efficacy and safety of gabapentin as monotherapy for treatment of partial onset seizures were evaluated in three large multicenter, double-blind, parallel-group, dose-controlled trials. In the first trial, 275 outpatients with refractory partial epilepsy maintained on stable doses of one or two antiepileptic drugs (AEDs) were switched to gabapentin (GBP) monotherapy at 600 mg, 1200 mg, or 2400 mg daily. Patients were required to exit the 26-week double-blind phase of the study if they experienced worsening of seizure frequency. With respect to time to exit, there was no statistically significant difference among the three groups; only 3% of patients withdrew from the trial because of adverse events. In the second study, 82 hospitalized patients with medically refractory epilepsy were tapered off baseline AEDs and randomly assigned to GBP monotherapy at 300 mg/day or 3600 mg/day. Patients remained in the trial for a maximum of 8 days but had to exit the trial if they experienced one or more exit events. Time to exit was significantly longer in patients in the 3600-mg group (151 h) compared with those in the 300-mg group (85 h) (p = 0.0001). None of the patients withdrew from the trial because of side effects. In the third study, 292 patients with newly diagnosed partial seizures were randomized to GBP 300, 900, or 1800 mg/day or to carbamazepine (CBZ) 600 mg/day. Patients remained in the trial for up to 6 months or until they experienced an exit event. Mean time to exit was significantly longer for patients who received GBP 900 mg/day (p = 0.02) or 1800 mg/day (p = 0.04) compared with those who received 300 mg/day. The completion rate for the CBZ group (37%) was similar to that of the GBP 900-mg (39%) and 1800-mg (38%) groups. Patients receiving CBZ had a higher withdrawal rate because of adverse events compared with the GBP 900-mg and 1800-mg groups. The results of these trials provide good evidence of the efficacy and safety of GBP as monotherapy for the treatment of partial-onset seizures.
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We used the database of a therapeutic drug monitoring unit at a tertiary epilepsy referral center to identify patients who had PMP as part of their treatment and extracted clinical information from their medical notes. Sera PMP concentrations were determined using liquid chromatography/mass spectroscopy.
Piperine, is the major active principal of black pepper. In traditional medicine, black pepper has been used as an analgesic, anti-inflammatory agent and in the treatment of epilepsy. This study was conducted to evaluate the in vivo analgesic and anticonvulsant effects of piperine in mice. The analgesic and anticonvulsant effects of piperine were studied in mice using acetic acid-induced writhing, tail flick assay, pentylenetetrazole (PTZ)- and picrotoxin (PIC)-induced seizures models. The intraperitoneal (i.p.) administration of piperine (30, 50 and 70 mg/kg) significantly inhibited (P<0.01) the acetic acid-induced writhing in mice, similar to the effect of indomethacin (20 mg/kg i.p.). In the tail flick assay, piperine (30 and 50 mg/kg, i.p.) and morphine (5 mg/kg, i.p.) caused a significant increase (P<0.01) in the reaction time of mice. Pre-treatment of animals with naloxone (5 mg/kg i.p.), reversed the analgesic effects of both piperine and morphine in the tail flick assay. Piperine (30, 50 and 70 mg/kg, i.p.) and standard drugs, valproic acid (200 mg/kg, i.p.), carbamazepine (30 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) significantly (P<0.01) delayed the onset of PTZ-and PIC-induced seizures in mice. These findings indicate that piperine exhibits analgesic and anticonvulsant effects possibly mediated via opioid and GABA-ergic pathways respectively. Moreover, piperine being the main constituent of black pepper, may be contributing factor in the medicinal uses of black pepper in pain and epilepsy.
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In the aquatic environment, pharmaceuticals have been widely found. Among them, carbamazepine and diclofenac were detected at the highest frequency. To evaluate the worldwide environmental impacts of both drugs, their global consumption volumes are estimated, based on the dose per capita. The metabolites of these pharmaceuticals are also of environmental concerns, especially trans-10,11-dihydro-10,11- dihydroxycarbamazepine (CBZ-diol) which probably has a similar concentration in water bodies to that of its parent drug. The removal efficiencies and mechanisms of both drugs in the wastewater treatment plants (WWTPs) are discussed with the actual state of knowledge. The occurrences of both drugs are examined in various water bodies including WWTP effluents, surface waters, groundwater and drinking water. Their chemical, physical and pharmacological properties are also addressed in context, which can largely influence their environmental behaviors. The ecotoxicological studies of both drugs imply that they do not easily cause acute toxic effects at their environmental concentrations. However their chronic effects need cautious attention.
Several antiepileptic drugs are available for the treatment of epileptic patients. However, the treatment of some seizure types and novel drug formulations deserve further advances in epilepsy research.
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An analytical method was developed to quantitatively determine pharmaceuticals in biosolid (treated sewage sludge) from wastewater treatment plants (WWTPs). The collected biosolid samples were initially freeze dried, and grounded to obtain relatively homogenized powders. Pharmaceuticals were extracted using accelerated solvent extraction (ASE) under the optimized conditions. The optimal operation parameters, including extraction solvent, temperature, pressure, extraction time and cycles, were identified to be acetonitrile/water mixture (v/v 7:3) as extraction solvent with 3 extraction cycles (15 min for each cycle) at 100 °C and 100 bars. The extracts were cleaned up using solid-phase extraction followed by determination by liquid chromatography coupled with tandem mass spectrometry. For the 15 target pharmaceuticals commonly found in the environment, the overall method recoveries ranged from 49% to 68% for tetracyclines, 64% to 95% for sulfonamides, and 77% to 88% for other pharmaceuticals (i.e. acetaminophen, caffeine, carbamazepine, erythromycin, lincomycin and tylosin). The developed method was successfully validated and applied to the biosolid samples collected from WWTPs located in six cities in Michigan. Among the 15 target pharmaceuticals, 14 pharmaceuticals were detected in the collected biosolid samples. The average concentrations ranged from 2.6 μg/kg for lincomycin to 743.6 μg/kg for oxytetracycline. These results indicated that pharmaceuticals could survive wastewater treatment processes, and accumulate in sewage sludge and biosolids. Subsequent land application of the contaminated biosolids could lead to the dissemination of pharmaceuticals in soil and water environment, which poses potential threats to at-risk populations in the receiving ecosystems.
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4-Aminopyridine (4-AP) is a convulsing agent that in vivo preferentially releases Glu, the most important excitatory amino acid neurotransmitter in the brain. Here the ionic dependence of 4-AP-induced Glu release and the effects of several of the most common antiepileptic drugs (AEDs) and of the new potential AED, vinpocetine on 4-AP-induced Glu release were characterized in hippocampus isolated nerve endings pre-loaded with labelled Glu ([3H]Glu). 4-AP-induced [3H]Glu release was composed by a tetrodotoxin (TTX) sensitive and external Ca2+ dependent fraction and a TTX insensitive fraction that was sensitive to the excitatory amino acid transporter inhibitor, TBOA. The AEDs: carbamazepine, phenytoin, lamotrigine and oxcarbazepine at the highest dose tested only reduced [3H]Glu release to 4-AP between 50-60%, and topiramate was ineffective. Vinpocetine at a much lower concentration than the above AEDs, abolished [3H]Glu release to 4-AP. We conclude that the decrease in [3H]Glu release linked to the direct blockade of presynaptic Na+ channels, may importantly contribute to the anticonvulsant actions of all the drugs tested here (except topiramate); and that the significantly greater vinpocetine effect in magnitude and potency on [3H]Glu release when excitability is exacerbated like during seizures, may involve the increase additionally exerted by vinpocetine in some K+ channels permeability.
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Frontal lobe seizures have a tendency to occur in sleep and in most cases occur exclusively in sleep; these individuals are said to have nocturnal frontal lobe (NFLE). NFLE can be difficult to distinguish clinically from various other sleep disorders, particularly parasomnias, which also present with paroxysmal motor activity in sleep. Interictal and ictal EEG findings are frequently unremarkable or nonspecific in both parasomnias and NFLE making the diagnosis even more difficult. Nocturnal epilepsy should be suspected in patients with paroxysmal events at night characterized by high frequency, repetition, extrapyramidal features, and marked stereotypy of attacks. Here we present a 13-year-old female who was extensively worked up for choking episodes at night. On repeat video EEG she was found to have frontal opercular seizures. Once on Carbamazepine, her seizures completely resolved.
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An acute liver damage with jaun. dice and biochemical abnormalities developed in 16-year-old adolescent, affected by chronic hepatitis B, after 3 years of carbamazepine therapy. The maximum bilirubin concentration in the blood was 445 micromol/L and the highest activity of AST, ALT, PA, GTP were noted, 648 U/L, 1497 U/L, 312 U/L, 85 U/L respectively. INR was 1.59. The blood ammonia level was elevated to 60.9 micromol/L. The carbamazepine treatment was stopped and laboratory parameters improved.
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The purpose of the present project is to examine the applicability of certain natural biological and liquid membranes for the separation of drugs of environmental concern such as ibuprofen, diclofenac, carbamazepine, and sulfamethoxazol from dilute aqueous solutions. Different types of intestine parts of cattle, sheep, and pig were applied as biological flat sheet membranes after different modes of pretreatment. Best results were obtained with special parts of cattle appendix. The concentration of each drug in the aqueous feed phase was in the range of 0.1-10 mg (cm3)(-1), the pH-values adjusted between 8 and 10. Pure water was used as the permeation phase. The influence of experimental parameters such as stirring velocity, temperature, pH-value, salt concentration, and the presence of surfactants as well as humic substances was studied. Under all conditions chosen the combined drugs permeate simultaneously through the natural membranes as the permeation kinetics of the individual compounds are very similar, while humic compounds were retained. Additional treatment of the permeate with liquid or solid phase extraction techniques increases crucially the depletion of the drugs from the feed. The mass transfer of the pharmaceuticals through the liquid membranes was carried out in three-compartment transport cells and supported liquid membrane-chambers. The three-phase liquid bulk membrane systems consisted of an aqueous feed solution, an organic solvent (dihexyl ether, decane, undecane, or decanol) with and without a dissolved sulfonic acid, tertiary amine or Cu(II)-chelate compound as a liquid bulk membrane and an aqueous stripping solutions containing dilute solutiuons of Na2CO3, NaOH, HCl, or HClO4. The transport of the drugs shows some differences, which can be attributed to their acid/base-behavior and partition coefficients log Kow. High extraction yields were obtained for sulfamethoxazol and carbamazepine by using polar organic solvents. Maximum transport efficiencies were obtained for the acidic compounds ibuprofen and diclofenac. They were completely extracted by using dihexyl ether loaded with octane sulfonic acid. A pH-gradient between feed and strip increases the efficiency of the transport. Certain three-phase compositions were successfully utilized in supported liquid membrane systems (SLM) so that high enrichment factors (approximately 75) were achieved for traces of diclofenac and ibuprofen. The solid and liquid membrane systems employed aim for technical as well as analytical purposes, such as sample pretreatment prior to HPLC-UV or LC-MS analysis of drug traces.
A 33 yr old man, previously diagnosed with hypothyroidism, presented with decreased level of consciousness and generalized tonic-clonic (GTC) seizure to Namazi hospital, Shiraz, Iran, during April 2015. The patient later referred with another episode of seizure like attack for which he received phenytoin, carbamazepine and levothyroxine and was discharged. During his last admission, the patient was admitted with chief complaints of decreased consciousness and four GTC attacks. On admission, the patients had aphasia, ataxia, loss of verbal communication, eye contact and complete loss of obedience. Thyroid function tests showed low levels of T3 and T4 with high levels of thyroid stimulating hormone. Other blood tests were all either normal or slightly abnormal. Lumbar puncture and CSF analysis had a high titer of Anti-TPO antibodies. With high suspicion of Hashimoto encephalopathy, pulsed methyl prednisolone (10 mg) was administered, however the patient showed little improvement. Therefore, plasmaphresis was started, to which the patient showed dramatic response.
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Of the 51 children, 36 (males-21), were followed up and their data analyzed. Mean homocysteine level was 11.51±3.95 umol/L at recruitment and 11.77±6.65 umol/L at six months (P=0.785). At recruitment 6(16%) children had homocysteine level above 15 umol/L which increased to 10(27%) at 6 months. Mean vitamin B12 at recruitment was 292.1±111.2 pg/mL and 297.8±82.9 pg/mL at 6 months (P=0.764). Mean folic acid at recruitment was 9.98±3.45 ng/mL and 10.66±3.97 ng/mL at 6 months (P=0.358). There was no correlation between carbamazepine levels with homocysteine, vitamin B12 and folic acid (P>0.05). There was no effect of age, sex or dietary pattern on homocysteine levels.
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Fourteen epileptic women under chronic treatment receiving only the anticonvulsant CBZ to control their crises were studied. A blood sample was taken before breakfast, before the morning dose of 200 mg, and after the dose at 1, 2, 3, 4, 5, and 8 h. Serum was separated by centrifugation at 1,350 x g. Serum concentrations of carbamazepine (CBZ) and of the metabolite carbamazepine 10,11-epoxide (CBZ-E) were measured by HPLC. Pharmacokinetic parameters were calculated by statistical moment method after obtaining serum concentrations.