Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies.

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Benedetti MS

Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies.

Fundam Clin Pharmacol. 2000 Jul-Aug;14(4):301-19. doi: 10.1111/j.1472-8206.2000.tb00411.x.

PubMed ID

11030437 [ View in PubMed

]

Abstract

The aim of this paper is to review a number of new antiepileptic agents (i.e. felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide) for their inducing and/or inhibitory properties in humans, mainly considering the interactions where they are involved as the cause rather than the object of such interactions. Two aspects have been particularly taken into account: the changes or absence of changes in plasma/serum concentrations of concomitant drugs and the direct or indirect evidence of induction, inhibition or lack of effect on the six major human hepatic CYP isozymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4), as well as on other CYP isozymes or enzyme systems. Felbamate clearly affects the pharmacokinetics of a number of drugs, generally increasing but also decreasing their concentrations. It induces enzymes such as CYP3A4 and inhibits enzymes such as CYP2C19 and those of the beta-oxidation pathway. Topiramate is not devoid of potential interaction properties: it decreases the plasma concentrations of ethinylestradiol, induces CYP3A4 and inhibits CYP2C19. For oxcarbazepine, no inhibitory, only inductive effects have been observed thus far. Felbamate. topiramate and oxcarbazepine may induce the metabolism of steroidal oral contraceptives. In this respect, tiagabine has been studied at a rather low dose. Pharmacodynamic or pharmacokinetic interaction seems to exist between lamotrigine and carbamazepine. Lamotrigine appears to be a weak inducer of UGTs, whereas induction of CYP3A4 seems improbable as the compound does not change the concentrations of oral contraceptives or the urinary excretion of 6beta-hydroxycortisol. Zonisamide has very peculiar pharmacokinetics and an extensive metabolism. Additional information on its enzyme inducing or inhibiting properties would be necessary, as data so far collected on its effect on the pharmacokinetics of other drugs are conflicting. Gabapentin, vigabatrin and in particular levetiracetam appear to be devoid of significant enzyme inducing or inhibiting properties.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Topiramate	Cytochrome P450 3A4	Protein	Humans	Unknown	Inducer	Details

Drug Interactions

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

Drugs	Interaction
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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.
Primidone Felbamate	The serum concentration of Phenobarbital, an active metabolite of Primidone, can be increased when used in combination with Felbamate.