The ideal pharmacokinetic properties of an antiepileptic drug: how close does levetiracetam come?

Epileptic Disord. 2003 May:5 Suppl 1:S17-26.

Abstract

The pharmacokinetic properties of a drug are the primary deter-minant of the extent and duration of drug action, and influence susceptibility to clinically important drug interactions. Most of the older-generation antiepileptic drugs (AEDs) are far from ideal in terms of pharmacokinetics and interaction potential. For example, phenytoin, carbamazepine, and valproic acid exhibit non-linear kinetics; carbamazepine and valproic acid have relatively short half-lives; and most of these drugs cause either enzyme induction (phenytoin, phenobarbital, primidone, carbamazepine) or enzyme inhibition (valproic acid). Compared with older agents, certain new-generation AEDs offer a num-ber of pharmacokinetic advantages, particularly in terms of reduced inter-patient variability in drug clearance and a lower interaction potential. One of the most recently developed of these drugs, levetiracetam, comes especially close to fulfilling the desirable pharmacokinetic characteristics for an AED: (1) it has a high oral bioavailability, which is unaffected by food; (2) it is not significantly bound to plasma proteins; (3) it is eliminated partly in unchanged form by the kidneys and partly by hydrolysis to an inactive metabolite, without involvement of oxidative and conjugative enzymes; (4) it has linear kinetics; and (5) it is not vulnerable to important drug interactions, nor does it cause clinically significant alterations in the kinetics of concomitantly administered drugs. Although its half-life is relatively short (6 to 8 hours), its duration of action is longer than anticipated from its pharmacokinetics in plasma, and a twice-daily dosing regimen is adequate to produce the desired response.

Publication types

  • Review

MeSH terms

  • Acetates / pharmacokinetics
  • Acetates / therapeutic use
  • Amines*
  • Animals
  • Anticonvulsants / pharmacokinetics*
  • Anticonvulsants / therapeutic use*
  • Carbamazepine / analogs & derivatives*
  • Carbamazepine / pharmacokinetics
  • Carbamazepine / therapeutic use
  • Cyclohexanecarboxylic Acids*
  • Drug Interactions
  • Epilepsy / drug therapy*
  • Epilepsy / metabolism
  • Felbamate
  • Fructose / analogs & derivatives*
  • Fructose / pharmacokinetics
  • Fructose / therapeutic use
  • Gabapentin
  • Half-Life
  • Humans
  • Isoxazoles / pharmacokinetics
  • Isoxazoles / therapeutic use
  • Lamotrigine
  • Levetiracetam
  • Nipecotic Acids / pharmacokinetics
  • Nipecotic Acids / therapeutic use
  • Oxcarbazepine
  • Phenylcarbamates
  • Piracetam / analogs & derivatives*
  • Piracetam / pharmacokinetics*
  • Piracetam / therapeutic use*
  • Propylene Glycols / pharmacokinetics
  • Propylene Glycols / therapeutic use
  • Tiagabine
  • Topiramate
  • Triazines / pharmacokinetics
  • Triazines / therapeutic use
  • Vigabatrin / pharmacokinetics
  • Vigabatrin / therapeutic use
  • Zonisamide
  • gamma-Aminobutyric Acid*

Substances

  • Acetates
  • Amines
  • Anticonvulsants
  • Cyclohexanecarboxylic Acids
  • Isoxazoles
  • Nipecotic Acids
  • Phenylcarbamates
  • Propylene Glycols
  • Triazines
  • Topiramate
  • Fructose
  • Carbamazepine
  • Levetiracetam
  • Zonisamide
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Vigabatrin
  • Lamotrigine
  • Oxcarbazepine
  • Felbamate
  • Tiagabine
  • Piracetam