OBJECTIVETo study serum levels of melatonin in children with epilepsy or febrile seizures in order to provide a basis for the treatment of epilepsy or febrile seizures with melatonin.

METHODSSerum melatonin levels were measured using ELISA in 15 children with simple febrile seizure (SFS), in 15 children with complex febrile seizure (CFS), in 15 children with epilepsy, and in 15 children with upper respiratory infections (control group).

RESULTSSerum melatonin levels in children with epilepsy (8.66+/-1.38 ng/L) or CFS (14.91+/-2.61 ng/L) were significant lower than those in the control group (23.93+/-2.01 ng/L) (P<0.01). The SFS group showed lower serum melatonin levels (20.72+/-2.54 ng/L) compared with the control group, but there were no statistical differences between the two groups. Serum melatonin levels in the epilepsy group were significantly lower than those in the CFS (P<0.05) and the SFS groups (P<0.01).

CONCLUSIONSSerum melatonin levels decreased in children with epilepsy or CFS. Supplement of exogenous melatonin might be a promising treatment for epilepsy and febrile seizures in children.

Child ; Child, Preschool ; Epilepsy ; blood ; drug therapy ; Female ; Humans ; Infant ; Male ; Melatonin ; blood ; pharmacology ; therapeutic use ; Seizures, Febrile ; blood

OBJECTIVETo study the effects of valproate sodium (VPA) on the level and axle of pituitary gonadotropin in adolescent girls with epilepsy.

METHODSTwenty-three adolescent girls with epilepsy aged from 8 to 14 years were treated with VPA for 1 year. The levels of serum pituitary gonadotropin including estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin and testosterone were measured before treatment and 3 months, 6 months and 1 year after treatment.

RESULTSThe serum levels of estradiol, follicle-stimulating hormone, luteinizing hormone and prolactin in the children with epilepsy were not significantly different during the 1 year VPA treatment compared with pretreatment. However, the serum level of testosterone was reduced 1 year after treatment (0.4±0.3 ng/mL) compared with pretreatment (0.7±0.4 ng/mL) and 3 months after treatment (0.7±0.4 ng/mL) (P<0.05).

CONCLUSIONSVPA treatment for 1 year does not increase serum levels of androgen in adolescent girls with epilepsy, suggesting that VPA is an ideal choice of treatment for the girls.

Adolescent ; Anticonvulsants ; therapeutic use ; Child ; Epilepsy ; blood ; drug therapy ; Female ; Gonadotropins, Pituitary ; blood ; Humans ; Valproic Acid ; therapeutic use

In Japan, because the most common site of drowning among patients with epilepsy is the bathtub, showering is generally recommended as an alternative to bathing. We herein report a case involving a female patient with epilepsy who drowned while showering. She had been diagnosed with epilepsy approximately 25 years previously, and her condition had progressed to refractory epilepsy. Carbamazepine, levetiracetam, lamotrigine, clobazam, and perampanel were prescribed daily. One day while showering, the patient was found lying with her face immersed in water that had accumulated on the floor of the bathtub. A forensic autopsy revealed water in the stomach, trachea, and proximal regions of both lung bronchi as well as white and red foam on the pharynx and larynx. A total of 1.9 μg/mL of lamotrigine, 0.14 μg/mL of carbamazepine, and 0.069 μg/mL of perampanel were detected in the patient's blood. The patient's cause of death was determined to be drowning due to an epileptic seizure. Although the patient was prescribed five types of antiepileptic medication, only three were detected in her blood. The current case demonstrates that drowning can occur while showering, suggesting that it is unsafe for patients with medication nonadherence. To prevent unintentional deaths in the bathroom, we recommend that patients with epilepsy maintain high adherence to all prescriptions and are supervised by a family member, even when showering. The current case is the first autopsy report of a patient with epilepsy who drowned while showering.
Adult ; Anticonvulsants ; blood ; therapeutic use ; Autopsy ; Drowning ; etiology ; pathology ; Drug Resistant Epilepsy ; drug therapy ; pathology ; Female ; Humans ; Japan ; Medication Adherence

To investigate the effects of carbamazepine (CBZ) on the plasma concentrations of valproic acid (VPA) and its toxic metabolite 2-propyl-4-pentenoic acid (4-ene VPA) in epileptic patients, the plasma concentrations of VPA and 4-ene VPA were determined, and the effect of CBZ on pharmacokinetics of VPA was evaluated. All patients had been divided into two groups (VPA group, n = 87; and VPA+CBZ group, n = 19). As compared to VPA group, the combination of CBZ significantly (P < 0.01) decreased the trough concentration of VPA [VPA group, (69.5 +/- 28.8) microg x mL(-1); VPA+CBZ group, (46.3 +/- 25.6) microg x mL(-1)] and does-adjusted VPA trough concentration [VPA group, (4.89 +/- 2.21) microg x mL(-1) x mg(-1) x kg(-1); VPA+CBZ group, (3.14 +/- 1.74) microg x mL(-1) x mg(-1) x kg(-1)]. However, the addition of CBZ did not influence the concentration of 4-ene VPA. The present study revealed that coadministration of CBZ can reduce VPA plasma concentration and may impact VPA clinical effect, therefore therapeutic drug mornitoring of VPA should be used when combined use of CBZ and VPA.
Adolescent ; Adult ; Anticonvulsants ; blood ; pharmacokinetics ; therapeutic use ; Carbamazepine ; blood ; pharmacokinetics ; therapeutic use ; Drug Interactions ; Drug Therapy, Combination ; Epilepsy ; blood ; drug therapy ; Fatty Acids, Monounsaturated ; blood ; Female ; Humans ; Male ; Valproic Acid ; blood ; pharmacokinetics ; therapeutic use ; Young Adult

PURPOSE: The pharmacokinetics of phenytoin is complicated by genetic and environmental differences. It is, therefore, important to monitor the serum concentrations in patients who receive phenytoin. Because most of the phenytoin in serum is bound to proteins, the level of serum albumin influences the amount of free phenytoin. MATERIALS AND METHODS: We compared the measured and calculated free phenytoin levels in epileptic patients who were taking phenytoin monotherapy, using the Sheiner-Tozer equation. A total of 49 patients (30 men and 19 women; age range, 15 - 87 years) were included in the study and their trough serum phenytoin and albumin concentrations were analyzed. RESULTS: The linear correlation between free and total phenytoin concentrations was moderate (r = 0.822, p < 0.001). The mean difference between measured and calculated free phenytoin was large (0.65 +/- 0.88 microg/mL; 95% confidence interval (CI), -1.11 to 2.41). After dividing the patients into groups by albumin concentration, hypoalbuminemic patients (< 3.5 g/dL) more often had a greater percent difference (> or = 20%) than observed in the normoalbuminemic (> or = 3.5 g/dL) group. CONCLUSION: In hypoalbuminemic patients, the measurement of free phenytoin level is necessary to properly evaluate the phenytoin level than that calculated from total phenytoin level.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anticonvulsants/*blood/pharmacokinetics/therapeutic use ; Epilepsy/*blood/drug therapy ; Female ; Humans ; Male ; Middle Aged ; Phenytoin/*blood/pharmacokinetics/therapeutic use ; Young Adult

Adolescent ; Anticonvulsants ; therapeutic use ; Body Mass Index ; Child ; Child, Preschool ; Epilepsy ; blood ; drug therapy ; Female ; Galanin ; blood ; Humans ; Infant ; Male ; Valproic Acid ; blood ; therapeutic use

OBJECTIVEAge, body weight and dose have been shown as important influencing factors for sodium valproate plasma concentrations. However it is unclear whether there is interaction among them and whether the interaction could influence sodium valproate plasma concentrations. This study aimed to evaluate the influence of age, body weight and dose on plasma concentrations of sodium valproate and the interaction among them.

METHODSOne hundred and thirty-two children with epilepsy (age: 4 months-6 years, weight: 5-25 kg) were enrolled. Sodium valproate was administered at the dosage of 10-30 mg/kg/d. Plasma concentrations of sodium valproate were measured by high-performance liquid chromatography 3-5 days after administration. The relationship of sodium valproate plasma concentrations with age, body weight, and dose of sodium valproate was examined using variance analysis, pearson correlation analysis and stepwise regression analysis.

RESULTSAge (F=8.630, P<0.01), body weight (F=3.650, P<0.05) and dose of sodium valproate (F=11.720, P<0.01) were influencing factors for sodium valproate plasma concentrations. The interaction between age and oral dose (F=2.484, P<0.05) and the interaction of age and body weight with oral dose (F=4.923, P<0.01) had significant effects on sodium valproate plasma concentrations. Stepwise regression analysis showed that dose of sodium valproate and body weight were entered to the regression equation.

CONCLUSIONSAge, body weight and dose of sodium valproate as well as the interactions between age and dose and between age, body weight and dose were influencing factors for valproate plasma concentrations.

Age Factors ; Anticonvulsants ; blood ; Body Weight ; Child ; Child, Preschool ; Epilepsy ; drug therapy ; Female ; Humans ; Infant ; Male ; Regression Analysis ; Valproic Acid ; administration & dosage ; adverse effects ; blood

OBJECTIVETo assess bone health in epileptic children who have been treated with topiramate (TPM) or carbamazepine (CBZ).

METHODSSixty-three epileptic children who received TPM or CBZ treatment and 36 eileptic children who did not receive any drug treatment (control group) were enrolled. Bone mineral density (BMD) at lumbar vertebrae (L1-L4) and radius-ulna was evaluated by the dual-energy X-ray absorptiometry method. Biochemical indices of bone metabolism, including serum calcium, phosphorus and alkaline phosphatase contents were measured.

RESULTSThe serum calcium content was higher in the TPM group (2.41+/-0.17 mmol/L), but it was lower in the CBZ group (2.15+/-0.26 mmol/L) than that (2.26+/-0.11 mmol/L) in the control group (p<0.05). The serum phosphorus content in both the TPM (1.55+/-0.17 mmol/L) and the CBZ groups (1.52+/-0.26 mmol/L) was significantly lower than that in the control group (1.70+/-0.30 mmol/L) (p<0.05). There were no significant differences in the serum content of alkaline phosphatase between three groups. BMD was significantly reduced in both the TPM and the CBZ groups when compared to the control group (p<0.05).

CONCLUSIONSTPM and CBZ may result in alterations in serum contents of calcium, phosphorus and alkaline phosphatase as well as BMD reduction.

Adolescent ; Alkaline Phosphatase ; blood ; Anticonvulsants ; adverse effects ; Bone Density ; drug effects ; Bone and Bones ; drug effects ; metabolism ; Calcium ; blood ; Carbamazepine ; adverse effects ; Child ; Child, Preschool ; Epilepsy ; drug therapy ; metabolism ; Female ; Fructose ; adverse effects ; analogs & derivatives ; Humans ; Male ; Phosphorus ; blood

We investigated the single- and multiple dose pharmacokinetics of a new controlled-release formulation (Orfil retard enteric coated tablet) of valproic acid in comparison with those of the plain tablet as a reference. Twelve healthy volunteers were given each formulation of 300 mg in the single-dose study. In the steady-state multiple-dose study, twelve epileptic patients received 1200 mg/day of the reference drug (300 mg 9 AM, 300 mg 3 PM, 600 mg 9 PM) and the test formulation (600 mg 9 AM, 600 mg 9 PM) with at least one week interval in cross-over manner. The AUC values of the test controlled release formulation were 91.7% (95% confidence interval: 78.4-100.4%) of the reference drug in the single-dose study and 98.2% (95% confidence interval: 86.2%-109.9%) in the steady-state study. The AUC's of the two formulations were not significantly different by ANOVA test. The Cmax and Tmax values of the test formulation were significantly different from the values of the reference in single-(Tmax: 158.4%, Cmax: 52.5% of the reference) and multiple-dose study (Tmax: 153.5% of the reference). The MRT values of the test formulation were also significantly greater (129.4% of the reference) in the single-dose study. Regarding the controlled-release characteristics of the test formulation, fluctuation index and percentage fluctuation of the twice a day dosage regimen of the test formulation were comparable with those of the thrice a day dosage regimen of the conventional tablet. Area deviation was even smaller in the test regimen of the controlled release formulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral ; Adult ; Biological Availability ; Delayed-Action Preparations ; Epilepsy/blood/*drug therapy ; Humans ; Male ; Tablets ; Tablets, Enteric-Coated ; Valproic Acid/*pharmacokinetics

OBJECTIVETo study the changes and significance of NF-kappa B activation in peripheral blood mononuclear cells (PBMC) of children with epilepsy.

METHODSNF-kappa B activation in PBMC was assayed by the flow cytometry in 32 healthy children and 64 children with epilepsy before and after treatment. The 64 epileptic children were subdivided into three groups: systemic seizure, partial seizure and unknown classification.

RESULTSNF-kappa B activation in PBMC in three epilepsy subgroups were significantly higher than that in healthy controls. The systemic seizure group showed significantly increased NF-kappa B activation in PBMC compared with the partial seizure group (p<0.01) and the unknown classification group (p<0.05). After treatment NF-kappa B activation in PBMC in three epilepsy subgroups was significantly reduced (p<0.01).

CONCLUSIONSNF-kappa B activation in PBMC increased in children with epilepsy, and it was positively correlated with the severity of seizures.

Adolescent ; Child ; Child, Preschool ; Epilepsy ; blood ; drug therapy ; Female ; Flow Cytometry ; Humans ; Infant ; Leukocytes, Mononuclear ; metabolism ; Male ; NF-kappa B ; metabolism