Pharmacokinetic interactions with felbamate. In vitro-in vivo correlation.
Article Details
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Glue P, Banfield CR, Perhach JL, Mather GG, Racha JK, Levy RH
Pharmacokinetic interactions with felbamate. In vitro-in vivo correlation.
Clin Pharmacokinet. 1997 Sep;33(3):214-24. doi: 10.2165/00003088-199733030-00004.
- PubMed ID
- 9314612 [ View in PubMed]
- Abstract
This article provides an analysis of the degree of agreement between in vivo interaction studies performed in patients with epilepsy and healthy individuals, and in vitro studies which identified the cytochromes P450 (CYP) inhibited by felbamate and those involved in its metabolism. In vitro studies show that felbamate is a substrate for CYP3A4 and CYP2E1. Compounds which induce CYP3A4 (e.g. carbamazepine, phenytoin and phenobarbital) increase felbamate clearance. However, the CYP3A4 inhibitors gestodene, ethinyl estradiol and erythromycin have little or no effect on felbamate trough plasma concentrations, consistent with the fact that the pathway is relatively minor for felbamate under normal (non-induced) conditions. Felbamate has been shown in vitro to inhibit CYP2C19, which would account for its effect on phenytoin clearance, and it had been postulated that this could be the mechanism underlying the reduced clearance of phenobarbital by felbamate. Although not yet examined in vitro, felbamate appears to induce the activity of CYP3A4, which would account for it reducing plasma concentrations of carbamazepine or the progestin gestodene. Interactions involving felbamate and non-CYP450-mediated metabolic pathways have also been addressed in clinical studies. The reduction in valproic acid (valproate sodium) clearance by felbamate is through the inhibition of beta-oxidation. No clinically relevant pharmacokinetic interactions were noted between felbamate and lamotrigine, clonazepam, vigabatrin, nor the active monohydroxy metabolite of oxcarbazepine. Information on the mechanisms underlying felbamate's drug:drug interaction profile permits predictions to be made concerning the likelihood of interactions with other compounds.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Felbamate Cytochrome P450 2C9 Protein Humans UnknownInhibitorDetails Felbamate Cytochrome P450 2E1 Protein Humans UnknownSubstrateDetails Felbamate Cytochrome P450 3A4 Protein Humans UnknownSubstrateInducerDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareFosphenytoinFelbamate The serum concentration of Fosphenytoin can be increased when it is combined with Felbamate. MethylphenobarbitalFelbamate The serum concentration of Phenobarbital, an active metabolite of Methylphenobarbital, can be increased when used in combination with Felbamate. PhenobarbitalFelbamate The serum concentration of Phenobarbital, an active metabolite of Phenobarbital, can be increased when used in combination with Felbamate. PhenytoinFelbamate The serum concentration of Phenytoin can be increased when it is combined with Felbamate. PrimidoneFelbamate The serum concentration of Phenobarbital, an active metabolite of Primidone, can be increased when used in combination with Felbamate.