Flucloxacillin instantly decreases serum levels of valproic acid: A case report.

Valproic acid (VPA) is used for epilepsy and bipolar disorder. It has near-complete bioavailability and is primarily metabolized by glucuronosyltransferases and mitochondrial oxidation. This case highlights a 79-year-old male with bipolar disorder on VPA therapy that started with flucloxacillin for Staphylococcus aureus bacteraemia and exhibited significantly reduced VPA serum levels. During hospitalization, flucloxacillin treatment correlated with a sharp decline of 75% in VPA total serum levels, a novel drug-drug interaction not previously reported. Nonadherence and absorption issues of VPA were ruled out, confirming flucloxacillin's role in reducing VPA levels. Because free-fraction serum levels of VPA remained within therapeutic range (5-25 mg/L) and our patient's bipolar disorder remained stable at 1000 mg twice daily, a dose increase was not necessary. Previous reports described cytochrome P450 enzyme induction as the mechanism of flucloxacillin lowering serum levels of immunosuppressants and antimycotics. Because only 10% of VPA is metabolized by cytochrome P450 enzymes, this is not plausible for this case. The proposed mechanism for the VPA-flucloxacillin drug-drug interaction is flucloxacillin as inducer of glucuronosyltransferase enzymes via the pregnane X receptor pathway, accelerating VPA metabolism. Because this case showed that free-fraction serum levels remained within therapeutic range, it underscores the need for free-fraction VPA monitoring in bipolar disorder and flucloxacillin therapy. When VPA is used for epilepsy, it is advised to consider alternative antibiotics to avoid this interaction.

A simple and sensitive methodology for voltammetric determination of valproic acid in human blood plasma samples using 3-aminopropyletriethoxy silane coated magnetic nanoparticles modified pencil graphite electrode.

In this work, we have prepared a nano-material modified pencil graphite electrode for the sensing of valproic acid (VA) by immobilization 3-aminopropyletriethoxy silane coated magnetic nanoparticles (APTES-MNPs) on the pencil graphite surface (PGE). Electrochemical studies indicated that the APTES-MNPs efficiently increased the electron transfer kinetics between VA and the electrode and the free NH2 groups of the APTES on the outer surface of magnetic nanoparticles can interact with carboxyl groups of VA. Based on this, we have proposed a sensitive, rapid and convenient electrochemical method for VA determination. Under the optimized conditions, the reduction peak current of VA is found to be proportional to its concentration in the range of 1.0 (±0.2) to 100.0 (±0.3) ppm with a detection limit of 0.4 (±0.1) ppm. The whole sensor fabrication process was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods with using [Fe(CN)6]3-/4-as an electrochemical redox indicator. The prepared modified electrode showed several advantages such as high sensitivity, selectivity, ease of preparation and good repeatability, reproducibility and stability. The proposed method was applied to determination of valproic acid in blood plasma samples and the obtained results were satisfactory accurate.

Changes of canonical Wnt signaling pathway in brains of rats with autism induced by prenatal exposure to valproic acid / 中国病理生理杂志

[ABSTRACT]AIM:ToinvestigatetherolesofthecanonicalWntpathwayinautism.METHODS:Usinganau-tistic model induced by prenatal exposure to valproic acid ( VPA) , we detected the expression of the signaling molecules of the canonical Wnt pathway in the prefrontal cortex (PFC) and hippocampus formation (HF) of autistic rats.The expres-sion levels of glycogen synthase kinase 3β( GSK-3β) , phosphorylated GSK-3β, β-catenin and phosphorylated β-catenin were observed by Western blotting .The mRNA expression of GSK-3β, β-catenin, c-Myc and cyclin D1 was assessed by semi-quantitative RT-PCR.RESULTS:The results of Western blotting showed that inactivated GSK-3β(Ser9) phospho-rylation was significantly increased , and inhibitory β-catenin ( Ser33/37/Thr41 ) phosphorylation was obviously decreased compared with control group .The results of RT-PCR showed that the mRNA levels of β-catenin, c-Myc and cyclin D1 in-creased, and GSK-3βwas significantly enhanced in VPA-exposed rats compared with the controls .CONCLUSION: In-creased activity of canonical Wnt pathway in the PFC and HF of autistic rats may contribute to the susceptibility to autism .

Baller-Gerold syndrome: Further evidence for association with prenatal exposure to valproate.

Baller Gerold Syndrome (BGS) is a rare autosomal recessive disorder that is apparent at birth. The disorder is characterized by distinctive malformations of the skull and facial area and bones of the forearms and hands. We are reporting a new case of BGS in a 10-month-old female child born of an epileptic mother who was on sodium valproate during the initial months of pregnancy. The baby was born with premature closure of the metopic suture, unilateral radial aplasia with limb malformation and other congenital anomalies that conformed with the description of BGS. The parents and other family members were unaffected, karyotyping was normal and there was no history of consanguinity. Fetal valproate exposure has been previously reported as the cause of this fetal malformation syndrome, which is generally inherited as an autosomal recessive trait. The peculiar pregnancy history and the supporting literature on the effects of valproic acid on the fetus exposed in utero to it with numerous case reports in the literature referring to BGS as a result of fetal exposure to valproate made us conclude that this is indeed a case of BGS secondary to valproate-induced teratogenesis.