In this study, spectroscopic and chromatographic evidence is presented for the identification and characterization of the metabolites, valproyl glutamate (2-propylpentanoyl glutamate, VPA-GLU) and valproyl glutamine (2-propylpentanoyl glutamine, VPA-GLN) in the urine, serum, and cerebrospinal fluid (CSF) of patients on valproic acid (VPA) therapy. Moreover, the identification of valproyl glycin...

Young children are at increased risk for valproic acid (VPA) hepatotoxicity. Urinary organic acid profiles, as a surrogate of mitochondrial function, were obtained in children 1.9 to 17.3 years of age (n = 52) who were undergoing treatment with VPA for seizure disorders. Age-matched patients receiving treatment with carbamazepine (CBZ; n = 50) and healthy children not undergoing treatment (n = ...

The present study investigated the effect of valproic acid (VPA) on the inhibition of RET signaling and induction of apoptosis in human thyroid carcinoma cells. VPA inhibited the viability of ARO and WRO cells and also inhibited cyclin D1 and caused caspase-3 cleavage. VPA decreased the level of RET protein and blocked the activation of RET downstream targets including phosphorylated ERK, phosp...

The anticonvulsant valproic acid (VPA, 2-n-propylpentanoic acid) causes inhibition of the citric acid cycle and elevations of central nervous system (CNS) gamma-aminobutyric acid (GABA) levels, which correlates with anticonvulsant action. No unifying mechanism for these actions of VPA has won general acceptance. alpha-Ketoglutarate dehydrogenase complex (KDHC) is a critical control enzyme in th...

Valproic acid (VPA) is one of the most frequently used antiepileptic drugs for the treatment of focal and generalized epilepsies. VPA has been demonstrated to have a negative effect on both the intrinsic and extrinsic coagulation systems. This article focusses on VPA induced fibrinogen reduction and hypofibrinogenemia. We systemically analyzed the fibrinogen reduction after VPA treatment and th...

The liver toxicity of valproic acid (VPA) is an established side effect of this widely used antiepileptic drug, which is extremely problematic for patients with metabolic epilepsy and particularly epilepsy due to mitochondrial dysfunction. In the present report, we investigated the reason for liver mitochondrial toxicity of VPA and several acid and amide VPA analogues. While the pyruvate and 2-...

        A simple, reproducible and rapid gas chromatographic method for precise determination of valproic acid (VPA) in human plasma has been developed. Total time for sample preparation and GC analysis is less than 45 min. After plasma protein precipitation, VPA was extracted into chloroform with suitable recovery. By using Stabilwax®<span styl...

a simple, reproducible and rapid gas chromatographic method for precise determination of valproic acid (vpa) in human plasma has been developed. total time for sample preparation and gc analysis is less than 45 min. after plasma protein precipitation, vpa was extracted into chloroform with suitable recovery. by using stabilwax®-da capillary gc column, a symmetrical gas chromatographic peak was ...

.Although several cases of acute hepatic failure associated with the administration of valproic acid (VPA) have been reported, the pathogenesis of this problem remains unclear. We report the case of a 40 month old male with a chronic seizure disorder treated with VPA and phenytoin for two years, who developed sudden progressive neurological deterioration with evidence of increased intracranial ...

Free and total valproic acid (VPA) pharmacokinetic evaluation was carried out at steady state in six young epileptics who were also receiving other anticonvulsants. Subjects received their usual morning dose of VPA after an overnight fast. Blood samples for free and total VPA were taken prior to the dose and frequently thereafter for 12 hours. The calculated pharmacokinetic parameters for total...