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.
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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.
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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.
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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.
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I have been using Healthmatters.io since 2021. I travel all over the world and use different doctors and health facilities. This site has allowed me to consolidate all my various test results over 14 years in one place. And every doctor that I show this to has been impressed. Because with any health professional I talk to, I can pull up historical results in seconds. It is invaluable. Even going back to the same doctor, they usually do not have the historical results from their facility in a graph format. That has been very helpful.
Karin
Advanced Plan Member since 2020
What fantastic service and great, easy-to-follow layouts! I love your website; it makes it so helpful to see patterns in my health data. It's truly a pleasure to use. I only wish the NHS was as organized and quick as Healthmatters.io. You've set a new standard for health tracking!
Paul
Healthmatters Pro Member since 2024
As a PRO member and medical practitioner, Healthmatters.io has been an invaluable tool for tracking my clients' data. The layout is intuitive, making it easy to monitor trends and spot patterns over time. The ability to customize reports and charts helps me present information clearly to my clients, improving communication and outcomes. It's streamlined my workflow, saving me time and providing insights at a glance. Highly recommended for any practitioner looking for a comprehensive and user-friendly solution to track patient labs!
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For our professional users, Healthmatters provides intuitive tools that not only streamline analysis but also save valuable time when delving into your client's lab report history.
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If you are still determining whether Healthmatters support your lab results, the rule is that if you can test it, you can upload it to Healthmatters.
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It's as simple as this: if you can get a test done, you can upload it to Healthmatters and we can interpret results from any lab out there. If laboratories can analyze it, we can interpret it.
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For those who prefer assistance, we offer a "Data entry service" to help you input your data. Simply attach an image or file of your lab test results, and a qualified team member from our data entry team will add the results for you.
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We’ve crafted multiple ways for you to navigate your data, whether you're glancing at a single report or delving into your historical test reports.
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Yes, you can. When entering values for the biomarker, you will see an "Edit Range" button. Click this button, and you'll have the option to enter a custom range.
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