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Archives of Neurology Mar 1983Twenty-four adult outpatients with poorly controlled complex partial seizures were treated with valproic acid. Previous therapy with antiepileptic agents was continued...
Twenty-four adult outpatients with poorly controlled complex partial seizures were treated with valproic acid. Previous therapy with antiepileptic agents was continued to maintain stable plasma drug levels. Initially 12 patients experienced greater than 50% seizure reduction. Only five patients maintained longterm benefit. In the other seven patients a tolerance developed to valproic acid's efficacy. Duration of seizure control seemed to be a function of initial seizure frequency. Toxic effects were generally mild. No hepatotoxic effect was noted and no hematological abnormalities developed. Weight changes occurred in 17 patients (14 gained weight) and five patients experienced a postural tremor. Eighteen patients experienced nausea.
Topics: Adolescent; Adult; Anticonvulsants; Epilepsy, Temporal Lobe; Female; Humans; Male; Middle Aged; Valproic Acid
PubMed: 6403001
DOI: 10.1001/archneur.1983.04050030029004 -
Neurosciences (Riyadh, Saudi Arabia) Oct 2019Several studies have reported a variable benefit of valproic acid for the treatment of infantile spasm. However, valproic acid can also worsen spasms, as occurred with...
Several studies have reported a variable benefit of valproic acid for the treatment of infantile spasm. However, valproic acid can also worsen spasms, as occurred with this child who presented with post-traumatic seizure which evolved to spasms. The child was started on antiepileptic medications, including valproic acid, despite that spasms persisting. For this reason, she was admitted for adrenocorticotropic hormone therapy. The baseline electroencephalogram showed modified hypsarrhythmia, and the laboratory workup showed thrombocytopenia, which was attributed to the valproic acid. After the valproic acid cessation, the spasms and the hypsarrhythmic pattern resolved dramatically next day, and the intended adrenocorticotropic hormone therapy was not started. Eight months later, she was still free of spasms. In conclusion, though valproic acid might have a beneficial effect in some patients with infantile spasm, it might have a negative impact on spasms in some patients which warrants its discontinuation sooner than later during spasms treatment.
Topics: Anticonvulsants; Drug Administration Schedule; Female; Humans; Infant; Spasms, Infantile; Thrombocytopenia; Valproic Acid
PubMed: 31872811
DOI: 10.17712/nsj.2019.4.20190026 -
Journal of Chromatography. A Dec 2014Valproic acid (VA) is a branch chain fatty acid that is widely used to treat epilepsy and convulsion. Recent studies show that VA can also be used to treat migraine...
Derivatization oriented strategy for enhanced detection of valproic acid and its metabolites in human plasma and detection of valproic acid induced reactive oxygen species associated protein modifications by mass spectrometry.
Valproic acid (VA) is a branch chain fatty acid that is widely used to treat epilepsy and convulsion. Recent studies show that VA can also be used to treat migraine headaches, bipolar disorder, and other diseases such as Alzheimer disease. However, clinical treatment with VA may cause hepatotoxicity, bone marrow suppression, and hyperammonemic encephalopathy. Valproic acid is also a known human teratogen. Because of the potential cytotoxic effects of VA and its major metabolite, 2-propyl 4-pentenoic acid (4-ene VA), VA plasma concentrations must be closely monitored during clinical applications of VA in order to avoid severe side effects. This study developed a derivatization oriented strategy for increasing sensitivity in detecting VA in quantities as low as 20μL and its metabolites in human plasma. After micro-scale liquid-liquid extraction (MLLE) and micro-scale derivatization, VA and 4-ene VA were quantitated by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The linear ranges were 10-1000μM for VA and 5-500μM for 4-ene VA. All relative standard deviation (RSD) and relative error (RE) values obtained in intra- and inter-day analyses of VA and 4-ene VA were below 8%. The structures of VA and its metabolite derivatives were further identified by nano ultra performance liquid chromatographic system (nanoUPLC) coupled with tandem mass spectrometry (MS/MS). Since protein modifications induced by VA were also identifiable by nanoUPLC-MS/MS, these modifications may be useful biological indicators of a toxic reaction during clinical applications of VA.
Topics: Amino Acid Sequence; Calibration; Chromatography, High Pressure Liquid; Humans; Liquid Phase Microextraction; Molecular Sequence Data; Reactive Oxygen Species; Tandem Mass Spectrometry; Valproic Acid
PubMed: 25444248
DOI: 10.1016/j.chroma.2014.11.025 -
Drug Safety 1990Acute toxicity in the setting of valproic acid (valproate sodium) overdose is in most cases benign and readily reversible. However, serious toxicity has been reported.... (Comparative Study)
Comparative Study
Acute toxicity in the setting of valproic acid (valproate sodium) overdose is in most cases benign and readily reversible. However, serious toxicity has been reported. We present a case of accidental acute valproic acid overdose in a 26-month-old female, in whom serious neurological, metabolic, haematological and respiratory sequelae occurred. The major toxicity observed was delayed cerebral oedema. We also present data not previously reported, which describes the pharmacokinetic disposition of valproic acid and several of its metabolites during the course of this acute overdose. A comparison of an enzyme immunoassay and gas liquid chromatographic methodologies for measuring valproic acid in this setting is also presented. It appears that the 2-EN-valproic acid metabolite plays a role in the neurological toxicity.
Topics: Brain Edema; Child, Preschool; Chromatography, Gas; Drug Overdose; Female; Humans; Immunoenzyme Techniques; Valproic Acid
PubMed: 2106903
DOI: 10.2165/00002018-199005010-00006 -
Epilepsia Feb 2007
Topics: Female; Hair; Humans; Middle Aged; Valproic Acid; White People
PubMed: 17295639
DOI: 10.1111/j.1528-1167.2006.00933.x -
Therapeutic Drug Monitoring 1984Five adult epileptic patients received 1,000 mg of valproic acid (Depakene) in both the regular and the enteric-coated form. Serum valproic acid levels were determined... (Comparative Study)
Comparative Study
Five adult epileptic patients received 1,000 mg of valproic acid (Depakene) in both the regular and the enteric-coated form. Serum valproic acid levels were determined at suitable intervals after drug administration. Pharmacokinetic parameters were equivalent for both preparations except for an absorption lag with the enteric-coated form. The relative bioavailability of the two compounds was similar across the group of patients, although there were marked differences between individual subjects. Close supervision of valproic acid serum levels is suggested after a change in drug formulation.
Topics: Adult; Biological Availability; Capsules; Epilepsy; Female; Humans; Kinetics; Male; Tablets, Enteric-Coated; Valproic Acid
PubMed: 6424275
DOI: 10.1097/00007691-198403000-00005 -
Molecules (Basel, Switzerland) May 2021High performance liquid chromatography with ultra-violet detection (HPLC-UV) and gas chromatography-mass spectrometry (GC-MS) methods were developed and validated for...
High performance liquid chromatography with ultra-violet detection (HPLC-UV) and gas chromatography-mass spectrometry (GC-MS) methods were developed and validated for the determination of chlorambucil (CLB) and valproic acid (VPA) in plasma, as a part of experiments on their anticancer activity in chronic lymphocytic leukemia (CLL). CLB was extracted from 250 µL of plasma with methanol, using simple protein precipitation and filtration. Chromatography was carried out on a LiChrospher 100 RP-18 end-capped column using a mobile phase consisting of acetonitrile, water and formic acid, and detection at 258 nm. The lowest limit of detection LLOQ was found to be 0.075 μg/mL, showing sufficient sensitivity in relation to therapeutic concentrations of CLB in plasma. The accuracy was from 94.13% to 101.12%, while the intra- and inter-batch precision was ≤9.46%. For quantitation of VPA, a sensitive GC-MS method was developed involving simple pre-column esterification with methanol and extraction with hexane. Chromatography was achieved on an HP-5MSUI column and monitored by MS with an electron impact ionization and selective ion monitoring mode. Using 250 µL of plasma, the LLOQ was found to be 0.075 μg/mL. The accuracy was from 94.96% to 109.12%, while the intra- and inter-batch precision was ≤6.69%. Thus, both methods fulfilled the requirements of FDA guidelines for the determination of drugs in biological materials.
Topics: Antineoplastic Combined Chemotherapy Protocols; Calibration; Chlorambucil; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Valproic Acid
PubMed: 34068372
DOI: 10.3390/molecules26102903 -
Epilepsia Dec 1978Dipropylacetic acid (VPA, valproic acid) has been quantified in plasma and semen from rabbits and man using a new gas-liquid chromatographic assay. The drug assay is...
Dipropylacetic acid (VPA, valproic acid) has been quantified in plasma and semen from rabbits and man using a new gas-liquid chromatographic assay. The drug assay is rapid, sensitive and free from interference by VPA metabolites. The beta phase half-life of VPA in rabbits after an i.v. dose (50 mg/kg) was 56 +/- 6 min. The concentration of VPA in rabbit plasma was 17 to 30 times the concentration in rabbit semen. In man, 500 mg doses of the free acid, p.o., resulted in VPA concentrations in plasma that were 11 to 17 times the concurrent levels in semen. VPA, in concentrations up to 10(-3) M, did not influence the motility of rabbit spermatozoa in vitro.
Topics: Adult; Animals; Humans; Male; Metabolic Clearance Rate; Rabbits; Semen; Valproic Acid
PubMed: 367760
DOI: 10.1111/j.1528-1157.1978.tb05034.x -
Psychiatria Polska 1987
Review
Topics: Chemical and Drug Induced Liver Injury; Hematologic Diseases; Humans; Neoplasms; Psychotic Disorders; Psychotropic Drugs; Valproic Acid
PubMed: 3112824
DOI: No ID Found -
Biomedical Chromatography : BMC Jan 2020A novel and robust two-dimensional liquid chromatography with ultraviolet detection method (2D-LC-UV) was developed and validated for high-throughput determination of...
A novel and robust two-dimensional liquid chromatography with ultraviolet detection method (2D-LC-UV) was developed and validated for high-throughput determination of the concentrations of valproic acid (VPA) in human plasma. This 2D-LC system was composed of a first-dimensional LC column, a second-dimensional LC column and an intermediate transfer column. The sample was directly injected into the 2D-LC system after an easy protein precipitation treatment. After online preconcentration and primary separation by the first-dimensional column, the target was captured by an intermediate column and then transferred to second-dimensional column for analysis. The system transferred the target through "central cutting" mode whereby the drug peak was not subject to interference from the matrix. The analysis cycle time was completed within 7.0 min. Compared with other methods that have been developed, the analysis time was reduced and the operation was much easier without any derivatization. The calibration curve was linear over the 5.90-188.94 μg/ml range for the VPA concentrations. The intra-day and inter-day precisions were <5.6%. The recoveries were in the range from 95.2 to 98.0%. This method appears to be sensitive, precise, rapid and low-cost for the quantification of VPA in serum sample.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Chromatography, Liquid; Drug Stability; Humans; Limit of Detection; Linear Models; Middle Aged; Reproducibility of Results; Valproic Acid; Young Adult
PubMed: 31469425
DOI: 10.1002/bmc.4695