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7 - Interactions between antiepileptic drugs

from Part II - Pharmacokinetic interactions

Published online by Cambridge University Press:  07 September 2009

Theodor W. May
Affiliation:
Biochemisches Labor der Gesellschaft für Epilepsieforschung, Maraweg 13, Bielefeld, Germany
Jerzy Majkowski
Affiliation:
Foundation of Epileptology, Warsaw
Blaise F. D. Bourgeois
Affiliation:
Harvard University, Massachusetts
Philip N. Patsalos
Affiliation:
Institute of Neurology, London
Richard H. Mattson
Affiliation:
Yale University, Connecticut
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Summary

Summary

Old and new antiepileptic drugs (AEDs) are associated with a wide range of pharmacokinetic drug–drug interactions. The classic AEDs exert important inducing and inhibiting effects on old and new AEDs.

Phenobarbital (PB) concentrations are significantly increased by valproic acid (VPA) and to a variable degree also by phenytoin (PHT). PHT levels may be decreased or increased by PB, depending on the PB concentration. The protein binding of PHT is decreased by VPA. Enzyme-inducing AEDs decrease primidone concentrations, but increase the levels of its metabolite PB. Carbamazepine (CBZ) concentrations are decreased by PB and PHT, whereas its metabolite CBZ-10,11-epoxide (CBZ-E) may be increased by VPA. Concentrations of VPA are considerably decreased by enzyme-inducing AEDs such as PB, PHT or CBZ. Sulthiame, a rarely used AED, increases PHT levels. Methsuximide (MSM), another rarely used AED, inhibits the metabolism of PB and PHT, but induces the metabolism of lamotrigine (LTG) and oxcarbazepine (OXC).

New AEDs exert relatively few inhibiting or inducing effects on the classic AEDs and hardly any on the new AEDs. However, felbamate (FBM) increases concentrations of PHT, PB, VPA and of CBZ-E, but reduces concentrations of CBZ. OXC (and some other new AEDs) may also increase PHT, whereas vigabatrin reduces the serum levels of PHT by approximately 20%. OXC has less pronounced enzyme-inducing effects than CBZ; however, topiramate (TPM) and LTG may be lowered by OXC.

Type
Chapter
Information
Antiepileptic Drugs
Combination Therapy and Interactions
, pp. 111 - 138
Publisher: Cambridge University Press
Print publication year: 2005

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