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Clinical Pharmacokinetics

, Volume 33, Issue 3, pp 214–224 | Cite as

Pharmacokinetic Interactions with Felbamate

In Vitro-In Vivo Correlation
  • Paul Glue
  • Christopher R. Banfield
  • James L. Perhach
  • Gary G. Mather
  • Jagdish K. Racha
  • Rene H. Levy
Review Article Drug Interactions

Summary

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 has 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 β-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.

Keywords

Carbamazepine Valproic Acid Lamotrigine Vigabatrin Oxcarbazepine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Adis International Limited 1997

Authors and Affiliations

  • Paul Glue
    • 1
  • Christopher R. Banfield
    • 1
  • James L. Perhach
    • 2
  • Gary G. Mather
    • 3
  • Jagdish K. Racha
    • 3
  • Rene H. Levy
    • 3
  1. 1.Clinical PharmacologySchering-Plough Research InstituteKenilworthUSA
  2. 2.Wallace LaboratoriesCranfordUSA
  3. 3.Department of PharmacologyUniversity of WashingtonSeattleUSA

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