Valproate is an alternative drug in the treatment of complex partial seizures but may be considered for initial therapy in patients with partial and secondarily generalized seizures.
Valproate controls absence, myoclonic, and tonic-clonic seizures in generalized, idiopathic, and symptomatic epilepsy. It is most useful in typical absence seizures. Valproate is as effective as ethosuximide in patients with absence seizures alone and is variably effective in atypical absence seizures. Although some clinicians prefer valproate for absence seizures, the American Academy of Pediatrics (Committee on Drugs, 1982) recommended that it be reserved for use when therapeutic failure or intolerance to ethosuximide occurs, because valproate causes rare but potentially fatal hepatotoxicity.
Many neurologists consider valproate the drug of choice for patients with both absence and other generalized seizure types, including tonic-clonic convulsions. Its efficacy is about the same as in patients with the latter type alone.
Valproate is the drug of choice in myoclonic epilepsy, with or without generalized tonic-clonic seizures, including juvenile myoclonic epilepsy of Janz, that begins in adolescence or early adulthood. Photosensitive myoclonus is usually easily controlled. Valproate also is effective in the treatment of benign myoclonic epilepsy, postanoxic myoclonus, and, with clonazepam, in severe progressive myoclonic epilepsy that is characterized by tonic-clonic seizures as well. It also may be preferred in certain stimulus-sensitive (reflex, startle) epilepsies.
Although valproate may be effective for infantile spasms, it is relatively contraindicated in children whose spasms are due to hyperglycinemia or other underlying metabolic (mitochondrial) abnormalities. In general, atonic and akinetic seizures in patients with Lennox-Gastaut syndrome are difficult to control, but valproate is the drug of choice for treatment of mixed seizure types. Since this drug has been useful in some patients who are refractory to all other antiepileptic drugs, it may warrant a trial in nearly all nonresponsive patients regardless of seizure type.
-----------------
The plasma protein binding of valproate is saturable within the usual therapeutic range (approximately 90% at 75 μg/mL). Usual effective plasma concentrations range from 50−120 μg/mL.4 With a daily dose of more than 500 mg, plasma concentrations may not increase proportionately because clearance increases with an increase in the free fraction. Daily fluctuations (up to two times higher) in free fraction and clearance also occur as a result of displacement by free fatty acids or circadian influences; thus, when plasma concentrations are being monitored, samples should be taken at a uniform time. Many neurologists recommend measuring trough concentrations.
Valproate is eliminated almost exclusively by hepatic metabolism. The metabolic fate is complex. A variety of conjugation and oxidative processes are involved, including entry into pathways (eg, beta oxidation) normally reserved for endogenous fatty acids. As the dose is increased, mitochondrial beta oxidation becomes saturated and increased glucuronidation occurs.
Metabolites may contribute to both antiepileptic and hepatotoxic effects. The antiepileptic activity of valproate (including the time course) is poorly correlated with steady-state valproate plasma concentrations. One unsaturated metabolite, 2-n-propyl-4-pentenoic acid (4-ene-VPA), has been proposed as a key hepatotoxic metabolite. The formation of this metabolite is increased by concomitant use of phenytoin, phenobarbital, carbamazepine, and other drugs that induce cytochrome P450. Due to inhibition of the same enzyme system, valproic acid may cause elevated levels of clomipramine with resultant seizures when the two agents are co-administered.5
The half-life of valproate in adults is 12 to 16 hours. In epileptic patients receiving polytherapy, the half-life is approximately nine hours, although five hours has also been reported. The half-lives in school-age children and young adolescents are well within the range of values in adults. Elimination half-lives are longer in neonates and generally shorter during middle and late infancy. Although hepatic clearance is reduced, the half-life in geriatric patients is approximately 15 hours. This has been attributed to the larger free fraction observed in this age group, especially in those with hypoalbuminemia.
Low valproic acid concentration relative to these ranges may suggest inadequate dosing.
Because the concentration of valproic acid fluctuates considerably depending on the time from last dose, interpretation of the clinical significance of the valproic acid concentration must take into consideration the timing of the blood specimen. For this reason, 2 collections are sometimes made to assess the trough and peak concentrations.
Dosage which is too low or too high can fail to alleviate or even worsen a person's symptoms.
Understand and improve your laboratory results with our health dashboard.
Upload your lab reports and get interpretation today.
Our technology helps to understand, combine, track, organize, and act on your medical lab test results.
A high valproic acid concentration may be associated with toxic effects.
Because the concentration of valproic acid fluctuates considerably depending on the time from last dose, interpretation of the clinical significance of the valproic acid concentration must take into consideration the timing of the blood specimen. For this reason, 2 collections are sometimes made to assess the trough and peak concentrations.
Dosage which is too low or too high can fail to alleviate or even worsen a person's symptoms.
Interpret Your Lab Results
Upload your lab report and we’ll interpret and provide you with recomendations today.
Get StartedGet Started With Our Personal Plan
Advanced Plan
Unlimited Plan
Are You a Health Professional?
Get started with our professional plan
Welcome to Healthmatters Pro.
Save time on interpreting lab results with the largest database of biomarkers online. In-depth research on any test at your fingertips, all stored and tracked in one place. Learn more
Pro Plan
for health professionals
$45 per month
At HealthMatters, we're committed to maintaining the security and confidentiality of your personal information. We've put industry-leading security standards in place to help protect against the loss, misuse, or alteration of the information under our control. We use procedural, physical, and electronic security methods designed to prevent unauthorized people from getting access to this information. Our internal code of conduct adds additional privacy protection. All data is backed up multiple times a day and encrypted using SSL certificates. See our Privacy Policy for more details.
Acetone, Blood, Ammonia, Plasma, Anti GAD 65 Antibodies, Anti-DNase B Strep Antibodies, Antiadrenal Antibodies, Quant, Antinuclear Antibodies, IFA, Antistreptolysin O Ab, B-Type Natriuretic Peptide, Babesia duncani WA1 IgG IFA, C difficile Toxins A+B, EIA, Carbon Monoxide, Blood, Cold Agglutinin Titer, Quant, Copper, RBC, Dehydroepiandrosterone (DHEA), Ethanol, Blood, F078-IgG Casein, F079-IgG Gluten, F2-Isoprostane/Creatinine, Fats, Neutral, Fats, Total, Folate, Hemolysate, Folate, RBC, G-6-PD, Quant, G6PD, Galectin-3, Histamine Determination, Blood, Interleukin-8, Serum, Isopropanol, Blood, K080-IgE Formaldehyde, Lactic Acid, Plasma, M-Spike, M207-IgG Aspergillus niger, Manganese, Plasma, Manganese, RBC, Melanocyte-stimulating Hormone (MSH), Methanol, Blood, Myeloperoxidase (MPO), Neopterin, Serum, NT-proBNP, Rubella Antibodies, IgG, Sirolimus (Rapamune), Blood, Strongyloides IgG Antibody, Testost., F+W Bound, Thyroxine Binding Globulin, Toxoplasma gondii Ab, IgG, Valproic Acid (Depakote), Serum, Varicella Zoster IgG, Vasoactive Intestinal Polypeptide (VIP), Plasma, Vitamin K1, ZnT8 Antibodies