Valproate encephalopathy: Case series and literature review.

Valproate encephalopathy is one of the unusual and severe but treatable side effect. This research focuses on four female patients who had valproate medication for epilepsy and developed an increased frequency of seizures, exacerbated disruption of consciousness, gastrointestinal problems, cognitive dysfunction, ataxia, and psychobehavioral abnormalities. The patient's symptoms improved over time once sodium valproate was stopped. As a result, when using sodium valproate, one should be aware of the risk of sodium valproate encephalopathy and cease using the medication right once if any of the above symptoms of unknown etiology manifest clinically. We also go over the potential pathogenesis that lead to valproate encephalopathy and the heightened risk of encephalopathy from taking antiepileptic medications together. It was stressed how crucial it is to identify, diagnose, and treat sodium valproate encephalopathy as soon as possible.

Dynamic effects of miR-20a-5p on hippocampal ripple energy after status epilepticus in rats.

To determine the dynamic effects of miR-20a-5p on hippocampal ripple energy in rats after status epilepticus (SE). A lithium pilocarpine (LiCl-PILO)-induced rat model of status epilepticus (SE) was established, and the rats were divided into the normal control (Control, CTL), epileptic control (PILO), valproic acid (VPA + PILO), miR-20a-5p overexpression lentivirus vector (miR + PILO), sponges blocking lentivirus vector (Sponges + PILO), and scramble sequence negative control (Scramble + PILO) groups (n = 6). Electroencephalograms (EEGs) were used to analyze changes in hippocampal ripple energy before and after SE. Quantitative polymerase chain reaction (q-PCR) analysis showed that miR-20a-5p levels gradually increased after miR-20a-5p overexpression lentivirus vector injection into the lateral ventricle, and the miR-20a-5p levels were significantly higher than that in CTL group on days 7 and 36 (P < 0.001). The miR-20a-5p levels decreased significantly on days 7 and 36 after blocking by sponges lentivirus vector injected into the lateral ventricle (P < 0.001). After injection of PILO, the average ripple energy expression in each group gradually increased, and reached the peak before chloral hydrate injection (compared with 1 day before SE, P < 0.05). The ripple energy in the VPA + PILO and Sponges + PILO groups was significantly lower than that in the PILO group at 60 min and 70 min after PILO injection and before chloral hydrate injection (P < 0.05), and maintained lower until 2 h after chloral hydrate injection in VPA + PILO (P < 0.05). Compared with the VPA + PILO group, the mean ripple energy of the Sponges + PILO group had no difference at all time points (P ≥ 0.05). After SE, ripple distribution of space and energy is closely related to the occurrence of epilepsy. Inhibition of miR20a-5p expression can downregulate ripple oscillation energy during seizure.

Influence of methadone on the anticonvulsant efficacy of valproate sodium gabapentin against maximal electroshock seizure in mice by regulation of brain MDA TNF-α.

Methadone is the most frequently used opioid therapy worldwide, with controversial effects on oxidative stress homeostasis. This study investigated the effects of intraperitoneal (i.p.) co-administration of methadone (0.1, 0.3, 1, and 3 mg/kg) and valproate sodium (300 mg/kg) or gabapentin (50 mg/kg) in the mice maximal electroshock (MES)-induced seizure model. The adverse effect of drugs was assessed using the chimney test. The levels of tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) contents were measured in mice brains after a single seizure. Administration of methadone alone resulted in a significant reduction in the duration of hind limb extension (HLE) than that in the control group. Methadone pretreatment at doses of 0.1 and 0.3 mg/kg i.p. decreased, and at doses of 1 and 3 mg/kg i.p. had an increasing effect on anticonvulsant efficacy of gabapentin. Pretreatment with all doses of methadone significantly decreased the valproate anticonvulsive efficacy. At doses of 1 and 3 mg/kg i.p. methadone per se increased brain MDA levels after MES-induced seizure. Administration of methadone (0.3 mg/kg i.p.) enhanced and at 3 mg/kg decreased gabapentin effect on brain MDA level, but their co-treatment did not lead to further increase in MDA. Methadone at 0.3-3 mg/kg enhanced the effect of sodium valproate on MDA levels in the brain, but at all doses significantly potentiated its effect on brain TNF-α levels. The drugs did not produce any side effects on motor coordination in experimental animals. In conclusion, methadone showed different effects on anticonvulsant actions of gabapentin and valproate through regulation of brain levels of MDA and TNF-α.

Case Report: A Case of Valproic Acid-Induced Hyperammonemic Encephalopathy Associated With the Initiation of Lithium: A Re-duplicable Finding.

Introduction: Hyperammonemic encephalopathy (HAE) is a serious adverse effect of valproate semisodium, which is facilitated by the potential for drug interaction. However, despite frequent co-prescription of valproate semisodium and lithium, the role of this combination in the occurrence of HAE has not been defined in the literature. This case report concerns the occurrence of HAE concomitant with the initiation of lithium in a 29-year-old patient who had been placed on valproate semisodium for a schizoaffective disorder. Case Report: Due to a relapse while on a combined antipsychotic and mood-stabilizing therapy (paliperidone palmitate and valproate semisodium), a cross-taper from valproate semisodium to lithium was proposed. The initiation of lithium was accompanied by an acute confusional syndrome, an elevated serum valproate level and hyperammonemia suggestive of drug-induced HAE. The discontinuation of lithium and reduction of valproate semisodium led to neurological improvement, until a recrudescence of psychiatric symptoms justified a rechallenge of the combination within the framework of a new cross-taper. As soon as Lithium was re-initiated, an increase in the serum valproate level and hyperammonemia were again noted. Discussion: The mechanisms of valproate-related HAE involve various metabolic pathways. In this case, exploration of the iatrogenic hypothesis focused on the imputability of concomitant cannabis use and co-prescriptions of benzodiazepines, antipsychotics, and in all likelihood, mood stabilizers. Conclusion: Therefore, this case study suggests that Lithium plays a role in serum valproate level elevation, and supports the hypothesis of an association between an elevated serum valproate level, hyperammonemia and reversible encephalopathy. A more in-depth pharmacokinetic exploration would provide a better understanding of the mechanisms of these interactions and support for the benefit-risk balance associated with this frequent co-prescription.

Non-hyperammonaemia valproate-induced encephalopathy: A case report.

WHAT IS KNOWN AND OBJECTIVE: Valproate sodium is an effective antiepileptic drug (AED). Serious adverse effects of valproate sodium are uncommon. This case report illustrates the existence of non-hyperammonaemia valproate-induced encephalopathy. CASE DESCRIPTION: A 47-year-old woman with epilepsy who developed valproate-induced encephalopathy without hyperammonaemia after valproate sodium treatment, and the symptoms completely subsided after withdrawal of valproate sodium. WHAT IS NEW AND CONCLUSION: Early diagnosis and identification of the mechanisms of non-hyperammonaemia valproate-induced encephalopathy are important. Immediate discontinuation of valproate sodium results in rapid resolution of symptoms in these patients.

Unexpected elevation in valproic acid concentration and agranulocytosis in a patient with short-chain acyl-CoA dehydrogenase deficiency.

BACKGROUND: Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an autosomal recessive metabolic disorder or condition of fatty acid ß-oxidation, caused by mutations in the gene encoding SCAD (ACADS). We report an infant with SCAD deficiency who unexpectedly exhibited an extremely high blood concentration of valproic acid (VPA) and agranulocytosis. CASE REPORT: An 8-month-old girl was diagnosed with West syndrome (infantile spasms), and VPA was administered at the standard level of 25 mg/kg/day. However, the blood concentration of VPA rose unexpectedly to 230 µg/mL (two- to three-fold higher than the expected value), and continued to remain relatively high even after the dosage was reduced (7 mg/kg/day, blood concentration of 88 µg/mL). Furthermore, she presented with a high-grade fever with agranulocytosis (neutrophil 231/µL). The abnormal pharmacokinetics and toxicity of VPA raised the suspicion of possible inborn errors of metabolism in the fatty acid ß-oxidation pathway. Blood tandem mass spectrometry revealed a transient elevation of C4, and urine gas chromatography-mass spectrometry revealed a continuous elevation of ethylmalonate. Finally, gene analysis revealed compound heterozygous mutations, c.625G > A (p.G209S) and c.1031A > G (p.E344G), in ACADS. CONCLUSION: VPA should be avoided if a patient is suspected to have inborn errors of ß-oxidation including SCAD deficiency.

The efficacy of magnesium oxide and sodium valproate in prevention of migraine headache: a randomized, controlled, double-blind, crossover study.

Migraine is a disabling disorder that affects the quality of life of patients. Different medications have been used in prevention of migraine headache. In this study, we evaluated the effectiveness of magnesium oxide in comparison with valproate sodium in preventing migraine headache attacks. This is a single-center, randomized, controlled, crossover trial which is double-blind, 24-week, 2-sequence, 2-period, 2-treatment. After patient randomization into two sequences, the intervention group received magnesium oxide 500 mg and the control group received valproate sodium 400 mg two tablets each day (every 12 h) for 8 weeks. The primary efficacy variable was reduction in the number of migraine attacks and number of days with moderate or severe headache and hours with headache (duration) per month in the final of 8 weeks in comparison with baseline. Seventy patients were randomized and seven dropped out, leaving 63 for analysis. In an intention-to-treat analysis, 31 patients were in group 1 (magnesium oxide-valproate) and 32 patients were in group 2 (valproate-magnesium oxide). The mean number of migraine attacks and days per month was 1.72 ± 1.18 and 2.09 ± 1.70, with a mean duration of 15.50 ± 21.80 h in magnesium group and 1.27 ± 1.27 and 2.22 ± 1.96, with a mean duration 13.38 ± 14.10 in valproate group. This study has shown that 500 mg magnesium oxide appears to be effective in migraine prophylaxis similar to valproate sodium without significant adverse effect.

Inhibitory effect of valproate sodium on pain behavior in diabetic mice involves suppression of spinal histone deacetylase 1 and inflammatory mediators.

Anti-epileptic medications are included in the international guidelines for managing neuropathic pain. Valproate sodium (VPS) was recently described as "the forgotten analgesic" and has been reported to relief pain in various models of neuropathic pain. Some studies reported anti-inflammatory and histone deacetylase 1 (HDA1) inhibitory properties for sodium valproate. The aim of the current study was to investigate the modulatory effect of VPS on pain behavior and inflammatory reactions in alloxan-induced diabetic neuropathy focusing on HDA1 inhibition and glia reactivity. 28 Male Swiss albino mice were allocated into four groups, (1) vehicle group, (2) alloxan-diabetic group, (3 & 4) alloxan+VPS (25 or 50 mg/kg) groups. VPS was given daily for 5 weeks by oral gavage. Pain behavior demonstrated increased allodynia (von-Frey filaments) and hyperalgesia (hot-plate test) in alloxan-diabetic mice that was reduced significantly by at least one of VPS doses. Sciatic nerves in diabetic mice showed increased histopathology score, increased silver staining for the nerves-indicating myelopathy- and a decrease in immunostaining for nerve growth factor. Spinal cord of diabetic mice showed greater histopathologic score, increased CD11b and glia fibrillary acidic protein (GFAP) immunostaining than vehicle treated mice. Molecular investigations highlighted greater content of spinal histone deacetylases, tumor necrosis factor-α (TNF-α) and interlukin-1ß (IL1ß) that were favorably modified by VPS. Overall, the current data confirmed that the pain killing and anti-inflammatory activity of VPS is at least partly mediated through inhibition of spinal HDA1 and glia reactivity. These findings support the view of inviting antiepileptics for treating neuropathies.

Comparison of Pregabalin and Sodium Valproate in Migraine Prophylaxis: A Randomized Double-Blinded Study.

Patients suffering from headache, particularly migraine type, are among the most dissatisfied patients. The aim of this study was comparing the efficacy of pregabalin with valproate sodium, in preventing migraine headache. In a randomized, double-blinded study, adult patients eligible for prophylactic treatment (i.e., patients with 4-15 attacks per month in last two months) were recruited. Patients' demographic data, duration of symptoms, headache frequency (attacks per month) and intensity (based on visual analogue scale) and also drugs used to relief headache were recorded. The patients were randomly assigned to two groups; valproate sodium (200 mg two times daily) and pregabalin (50 mg two times daily). The patients were examined by neurology specialist monthly for three months and the related data were recorded. The Data were analyzed using SPSS version 21, with related statistical tests. Total number of 140 patients with recurrent migraine were entered into the study. Sixty-nine patients were assigned to group A and 71 to group B by the randomizing table. Inter-group analysis of data in two arms of the study showed that two medications were equally effective except that pregabalin was not significantly effective in reducing number of attacks during first month of therapy compared to baseline. This differences were not significant at second and third month of the study. Our study showed that pregabalin, has comparable efficacy with valproate sodium in reducing migraine frequency, intensity, and duration of attacks and could be an alternative for migraine prophylaxis.

Efficacy and safety of levetiracetam for adult seizure: a randomized controlled trial / 第二军医大学学报

Objective To evaluate the efficacy and safety of levetiracetam (LTA) for adult seizure (AS).Methods A randomized,double-blinded,double-dummy,positive drug controlled trial was conducted.One hundred and twenty eligible AS patients were randomly divided into two groups:intervention group and control group,with 60 in each group.Patients in the intervention group received LTA tablet plus valproate sodium mimetic tablet,and patients in the control group received valproate sodium tablet and LTA mimetic tablet.The treatment course was 26 weeks in both groups,and the patients was followed up for 3 months after the treatment.The outcomes included total efficacy rate,weekly epilepsy seizure frequency,seizure duration,quality of life (measured by QOLIE-31 Scale) and adverse events related to drugs after 1-3 days of treatment and at 3 months of follow-up.Results The weekly epilepsy seizure frequency,seizure duration and QOLIE-31 score were not significantly different between the two groups before treatment.The total efficacy rates after treatment and at 3 months of follow-up in the intervention group were 95.0％ (57/60) and 91.7％ (55/60),respectively,and were significantly higher than those in the control group of 71.7％ (43/60) and 63.3％ (38/60) (P＜0.01).The weekly epilepsy seizure frequency,seizure duration and QOLIE-31 score after treatment and at 3 months of follow-up were significantly different as compared with before treatment in both groups (P＜0.01);and there were significantly different between the two groups (P＜0.01).The adverse events after treatment were similar between both groups.Conclusion The efficacy of LAT is superior to the valproate sodium tablet for AS,with the less toxicity,and it can be clinical drug of choice for AS.

Efficacy and safety of levetiracetam for adult seizure: A randomized controlled trial / 第二军医大学学报

Objective To evaluate the efficacy and safety of levetiracetam (LTA) for adult seizure (AS). Methods A randomized, double-blinded, double-dummy, positive drug controlled trial was conducted. One hundred and twenty eligible AS patients were randomly divided into two groups: intervention group and control group, with 60 in each group. Patients in the intervention group received LTA tablet plus valproate sodium mimetic tablet, and patients in the control group received valproate sodium tablet and LTA mimetic tablet. The treatment course was 26 weeks in both groups, and the patients was followed up for 3 months after the treatment. The outcomes included total efficacy rate, weekly epilepsy seizure frequency, seizure duration, quality of life (measured by QOLIE-31 Scale) and adverse events related to drugs after 1-3 days of treatment and at 3 months of follow-up. Results The weekly epilepsy seizure frequency, seizure duration and QOLIE-31 score were not significantly different between the two groups before treatment. The total efficacy rates after treatment and at 3 months of follow-up in the intervention group were 95. 0% (57/60) and 91 7% (55/60), respectively, and were significantly higher than those in the control group of 71 7% (43/60) and 63. 3% (38/60) (P<0 01). The weekly epilepsy seizure frequency, seizure duration and QOLIE-31 score after treatment and at 3 months of follow-up were significantly different as compared with before treatment in both groups (P<3. 01); and there were significantly different between the two groups (P<3 01). The adverse events after treatment were similar between both groups. Conclusion The efficacy of LAT is superior to the valproate sodium tablet for AS, with the less toxicity, and it can be clinical drug of choice for AS.

An effective assessment of valproate sodium-induced hepatotoxicity with UPLC-MS and (1)HNMR-based metabonomics approach.

Valproate sodium is one of the most prescribed antiepileptic drugs. However, valproate sodium has various side effects, especially its toxicity on liver. Current markers for toxicity reflect mostly the late stages of tissue damage; thus, more efficient methods for toxicity evaluation are desired. To evaluate the toxicity of valproate sodium on liver, we performed both UPLC-MS and (1)HNMR-based metabonomics analysis of serum samples from 34 epileptic patients (age: 42.0±18.6, 18 male/16 female) after valproate sodium treatment. Compared to conventional markers, the serum metabolic profiles provided clear distinction of the valproate sodium induced normal liver function and abnormal liver function in epileptic patients. Through multivariate statistical analysis, we identified marker metabolites associated with the hepatotoxicity induced by valproate sodium, such as glucose, lactate, acetoacetate, VLDL/LDL, lysophosphatidylcholines, phosphatidylcholines, choline, creatine, amino acids, N-acetyl glycoprotein, pyruvate and uric acid. This metabonomics approach may provide effective way to evaluate the valproate sodium-induced toxicity in a manner that can complement current measures. This approach is expected to find broader application in other drug-induced toxicity assessment.

Effects of valproate sodium on extracellular signal-regulated kinase 1/2 phosphorylation following hippocampal neuronal epileptiform discharge in rats.

The aim of the present study was to investigate the effects of valproate sodium (VPAS) on the phosphorylation extracellular signal-regulated kinase 1/2 (ERK1/2) following hippocampal neuronal epileptiform discharge in rat neurons. The study used neurons from female and male neonate Sprague-Dawley (SD) rats (at least 24 h old), which were rapidly decapitated. Following the successful development of the epileptiform discharge cell model, the neurons were divided into two groups, the VPAS group and the control group. In the concentration-response experiment, the neurons were incubated with three different concentrations of VPAS (50, 75 and 100 mg/l) 30 min prior to the epileptiform discharge. The expression of phosphorylated ERK1/2 (p-ERK1/2) was examined using an immunofluorescence technique. In the time-response experiment, the neurons were incubated with VPAS (50 mg/l) and monitored at different time-points (30 min prior to the epileptiform discharge and 0 min, 30 min, 2 h and 6 h subsequent to epileptiform discharge), and western blotting was employed to measure the changes in p-ERK1/2 protein expression. No significant differences in the expression of p-ERK1/2 among the neurons treated with different concentrations of VPAS were identified in the concentration-response experiment. However, in the time-response experiment, the expression of p-ERK1/2 30 min prior to the epileptiform discharge was significantly lower compared with that at the other time-points. Furthermore, 50 mg/l VPAS was capable of decreasing the action potential frequency of the neuronal epileptiform discharge. ERK1/2 was excessively and persistently activated following the epileptiform discharge of the neurons. In addition, a low concentration of VPAS was effective at inhibiting the phosphorylation of ERK1/2 at an earlier period of neuronal epileptiform discharge.

Bone turnover markers in epileptic patients under chronic valproate therapy.

BACKGROUND: The effects of chronic valproic acid administration on bone health have been a matter of concern and controversy. In this study, the bone status following valproate intake was assessed by using several bone-related biochemical markers. MATERIALS AND METHODS: In this case-control study, 62 epileptic patients and 40 age- and gender-matched controls were enrolled. The patients had been under chronic valproate therapy (758 ± 29 mg/day) for at least the past 6 months, without any vitamin D/or calcium supplementation. Serum markers of bone turnover (carboxy-terminal telopeptide of type I collagen (CTX) and bone-specific alkaline phosphatase [BALP]), calcium, phosphorus, total alkaline phosphatase, and parathyroid hormone levels were measured in both groups. RESULTS: The markers of bone turnover as well as other measured bone biochemical parameters did not statistically differ between the two groups. CONCLUSION: Valproate therapy at the mentioned doses does not seem to change bone turnover in adult epileptic patients.

Topiramate versus Valproate Sodium as Adjunctive Therapies to a Combination of Lithium and Risperidone for Adolescents with Bipolar I Disorder: Effects on Weight and Serum Lipid Profiles.

OBJECTIVE: To compare the effects of topiramate versus valproate sodium as an add-on therapy to a combination of lithium and risperidone (Li+Ris) on body weight and serum lipid profile in children and adolescents with bipolar disorder. METHODS: In a single-blind randomized clinical trial, thirty children and adolescents with bipolar disorder type I in the manic or mixed phase, treated with the combination of Li+Ris at therapeutic doses for at least 4 weeks who had the indication of add-on therapy due to a recurrent episode; a partial response or non response in the current episode or relapse were included. Participants were randomly assigned to receive either topiramate or sodium valproate as the third drug add-on therapy for a total of 6 weeks. Weight, height and serum lipid profiles were determined at baseline and at the end of week 6. RESULTS: Differences in the mean levels of lipid profiles at baseline and after week 6 evaluation were not significant in both treatment groups. BMI z-score increased in both treatment groups, being significant only in the Li+Ris/Valproate group, increasing from (mean±SD) 0.38±0.55 to 0.72±1.23 (p<0.05). Between group changes in BMI z-score was not significant.Among the BMI percentile categories, participants in the normal weight subgroup showed a significant increase in BMI z-score during the 6 week trial, compared to overweight/obese subgroup, in both Li+Ris/Valproate and Li+Ris/Topiramate treatment groups. Elevated mean serum level of triglyceride and a high proportion of participants with elevated total cholesterol (≥ 170 mg/dl), triglyceride (≥ 110 mg/dl), and BMI percentile 85-<95 at baseline (before randomization) and at the end of 6 week study were noted. CONCLUSION: When topiramate and valproate sodium are used for six weeks as adjunctive treatment to a combination of Li+Ris, they act alike on lipid milieu of children and adolescents with bipolar disorder. Both Li+Ris/Valproate and Li+Ris/Topiramate therapies can lead to an increase in BMI z-score. This increase is statistically significant with Li+Ris/Valproate therapy. This suggests that topiramate could attenuate the ongoing weight gain from lithium and risperidone. In this study, the majority of participants who gained weight were those with BMI less than 85th percentile. This suggests that normal weight patients may have greater weight gain potential than overweight/obese patients.High proportion of metabolic abnormalities among the patients at baseline, which remained elevated throughout the trial, warrants cardiometabolic monitoring in this population.

Effect of valproate sodium on genito-endocrine secretion in maidens with epilepsy / 中华神经医学杂志

Objective To analyze the influence of anti-epileptic drug valproate sodium (VPA)on the level of sex hormone in maidens with epilepsy.Methods Forty-six maidens with epilepsy aged from 8 to 15 years,collected in our hospital from September 2009 to October 2011 and received VPA treatment for 12 months,were chosen in our study.The levels of testosterone,estradiol (E2) and follicle-stimulating hormone (FSH) were surveyed before medication and 3,6,12 months after medication.Results The levels of E2 and FSH in maidens with epilepsy during the 12 months of VPA medication showed no significant difference as compared with those before treatment (P＞0.05); but the level of testosterone 12 months after medication (0.5±0.4 ng/mL) decreased compared with that before treatment (0.8 ±0.3 ng/mL) and 3 months after medication (0.8±0.3 ng/mL) (P＜0.05).Conclusion VPA has little effect on sex hormone level of maidens with epilepsy,and VPA is the best solution of treating maidens with epilepsy.

Effects of valproate sodium on phosphorylatted cAMP responsive element binding protein after hippocampal neuronal epileptiform discharge in rat / 重庆医科大学学报

Objective:To investigate the effects of valproate sodium on P-CREB1 after hippocampal neuronal epileptiform discharge in rat.Methods:The neonate wistar rats were decapitated quickly to obtain the hippocampal neuron,Which were cultured in vitro,After the epileptiform discharge model of neuron was established,neurons were divided into control group,model group,low valproate dose group(50mg/L) and high dose group(100mg/L).Expression positions of P-CREB1 after epileptiform discharge were examined by immunofluorescence technique,and Western blot was used to examine the expression intensity of P-CREB1 in different group.Results:Through immunofluorescence,P-CREB1 was observed in the nucleus of each group,and the most intensive expression was found in model group.Through western blot,the expression tendency was found to be the same as the former Results,Moreover,after added valproate sodium,the expression of P-CREB1 decreased,and there was statistical significance of the difference between low valproate dose and high dose(P

Influence of Valproate Sodium on Neuroprotective Effects of Topiramate / 实用儿科临床杂志

Objective To study the influence of valproate sodium(VPA)on neuroprotective effects of topiramate(TPM).Methods For-ty-eight 3-4 week-old male Wistar rats were randomly divided into 4 groups of 12 rats each.Group A was negative control rats,and groups B-D were rat model of epilepsy,induced by pentylenetetrazol(PTZ).The rats in 2 experimental groups were adminstered intragastrically with TPM 40 mg/kg and TPM 40 mg/kg+ VPA 200 mg/kg;2 control groups(groups A and B)with the equal amount of distilled water administration.After 2-month administration,changes of the behavior,levels of serum neuron-specific enolase(NSE)and the pathological in hippocampus were examined.Results The level of NSE in the group of TPM were significantly lower than that in masculine group,but no difference between masculine group and the TPM plus VPA.The pathological change in hippocampus were abatement in the group of TPM.Conclusion TPM plus high dosage of VPA will impaire the neuroprotective effects of TPM.

Chemical compatibility of depacon(®) with medications frequently administered by intravenous y-site delivery in patients with epilepsy or head trauma.

OBJECTIVES: Intravenous Y-site administration of more than one medication through the same in-line catheter is a common practice used in the management of acute seizures. The objective of this study was to determine the compatibility of valproate sodium (Depacon(®); 2 or 20 mg/mL) with 13 medications that are frequently administered to manage seizures or are given to patients with an acute head injury who are at risk for developing post-traumatic epilepsy. METHODS: The study medications included atracurium, dexamethasone, diazepam, fosphenytoin, lorazepam, magnesium sulfate, mannitol, methyl-prednisolone, midazolam, pentobarbital, phenytoin, ranitidine, and thiopental. Equal volumes of valproate and each of the study drugs were admixed and immediately examined using several physiochemical criteria: Tyndall effect, color and pH change, gas evolution, and particle formation (HIAC/Royco liquid particle counter). Samples were also evaluated using HPLC analysis (C(18) column; methanol/tetrahydrofuran/ phosphate buffer; 44/1/55% v/v, at 1.5 mL/min; 50°C) with UV (190-400 nm) photodiode detection. The valproate peak (220 nm) was quantified by both peak area and height. Samples were analyzed within 5 minutes of admixture and were reassessed at 15 and 30 minutes. RESULTS: With the exception of diazepam, midazolam, and phenytoin, all of the remaining drugs were chemically compatible with valproate, both in 5% Dextrose Injection, USP(D5W) and in 0.9% Sodium Chloride Injection, USP (Normal Saline -NS). None of the compatible medications produced a significant pH change, discernible gas, particle formation, reduced valproate titer by HPLC analysis (coefficient of variability < 1.5%), or the temporal formation of unidentified UV absorbing (190-400 nm) peaks. CONCLUSIONS: Intravenous valproate is compatible with most agents employed in seizure management or used in patients at risk for seizures following head injury and is safe for concurrent Y-site drug administration.

Blood Drug Concentration Monitoring of Sustained-Release Valproate Sodium in Children with Epilepsy / 实用儿科临床杂志

Objective To explore the blood drug concentration monitoring of sustained-release valproate(DK)in children with epilepsy,focusing on the selection of sampling time and evaluation of the results.Methods Two hundred and seventy-one children taking DK and 155 children taking sodium valproate syrup(VPA Syr)were involved and their serum were taken when achieved steady state to determine the valproic acid level using fluorescence polarization immunoassay.They were divided into 4 groups,which were DK taken once daily group(DK qd group,126 children),DK taken once daily at night and sampled on morning group(DK qn group,26 children),DK taken every 12 h group(DK q12 h group,119 children),VPA Syr q12 h group(155 children).Determine the proportion of the blood drug concentration of each group below,ithin and above the therapeutic range for valproate(50-100 mg/L)were determined.The data were analyzed by t test.Results The Cmin of DK qd group were(73.09?19.91)mg/L,significantly lower from the serum concentration of DK qn and sampled on morning group [(94.94?25.44)mg/L](P0.05).Conclusions DK qn should sampled at night before the night dose.The Cmin of DK q12 h was higher according to the therapeutic range,it's favorable range still needs clinical practice.