Is valproate a CYP450 inducer?

Is valproate a CYP450 inducer?

Phenytoin,10 carbamazepine,23 phenobarbital,20 and primidone16 are potent, broad-spectrum inducers of CYP450 and UGT isoenzymes, whereas valproic acid/divalproex sodium/valproate sodium5-8 strongly inhibit UGT isoenzymes, CYP2C19, and epoxide hydrolase.

Does valproic acid induce CYP?

Valproic acid induces CYP3A4 and MDR1 gene expression by activation of constitutive androstane receptor and pregnane X receptor pathways. Drug Metab Dispos.

How is valproate metabolized?

Metabolic pathways of valproic acid. In adults, the majority of valproate dose is eliminated via glucuronidation and mitochondrial β-oxidation pathways, and about 15-20% of the dose is metabolized by CYP enzymes. In contrast, valproate metabolism is shifted towards CYP-dependent route in children.

Is valproate a CYP450 inhibitor?

Valproic acid inhibits the activity of CYP2C9 at clinically relevant concentrations in human liver microsomes. Inhibition of CYP2C9 can explain some of the effects of valproic acid on the pharmacokinetics of other drugs, such as phenytoin.

Is valproate an inducer or inhibitor?

Sodium valproate is a first generation AED that inhibits, rather induces, liver enzymes. It is an inhibitor of the UDP-glucuronosyltransferase (UGT) enzyme system, which is involved in the metabolism of androgens and estrogens [89].

Is valproate a cyp450 inhibitor?

Is valproic acid renally cleared?

Protein binding is decreased in patients with renal insufficiency, in patients with chronic liver disease, and possibly in the presence of other displacing agents. The total plasma clearance of valproic acid is in the range of 5 to 10ml/min.

How is Depakote metabolized?

Valproate is metabolized almost entirely by the liver. In adult patients on monotherapy, 30-50% of an administered dose appears in urine as a glucuronide conjugate. Mitochondrial β-oxidation is the other major metabolic pathway, typically accounting for over 40% of the dose.

What does cytochrome P450 metabolize?

Cytochrome P450 monooxygenases catalyze the oxidation and metabolism of a large number of xenobiotics and endogenous compounds. CYP450 enzymes evolved as the primary defense against xenobiotics and in this process are also responsible for the bioactivation of drugs and toxicants to more reactive intermediates.

Is valproate an enzyme inducer?

Valproic acid is not enzyme inducer, but it may cause clinically relevant drug interactions by inhibiting the metabolism of selected substrates, most notably phenobarbital and lamotrigine.

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