Pharmacokinetic interactions with felbamate. In vitro-in vivo correlation.

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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	Unknown	Inhibitor	Details
Felbamate	Cytochrome P450 2E1	Protein	Humans	Unknown	Substrate	Details
Felbamate	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inducer	Details

Drug Interactions

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drugs	Interaction
Integrate drug-drug interactions in your software
Fosphenytoin Felbamate	The serum concentration of Fosphenytoin can be increased when it is combined with Felbamate.
Methylphenobarbital Felbamate	The serum concentration of Phenobarbital, an active metabolite of Methylphenobarbital, can be increased when used in combination with Felbamate.
Phenobarbital Felbamate	The serum concentration of Phenobarbital, an active metabolite of Phenobarbital, can be increased when used in combination with Felbamate.
Phenytoin Felbamate	The serum concentration of Phenytoin can be increased when it is combined with Felbamate.
Primidone Felbamate	The serum concentration of Phenobarbital, an active metabolite of Primidone, can be increased when used in combination with Felbamate.