Terapéutico medicinal supervisión sobre el tratamiento de la epilepsia

Antiepileptic drugs—best practice guidelines for

therapeutic drug monitoring: A position paper by the

subcommission on therapeutic drug monitoring, ILAE

Commission on Therapeutic Strategies

∗Philip N. Patsalos, †David J. Berry, ‡Blaise F. D. Bourgeois, §James C. Cloyd,

¶Tracy A. Glauser, #Svein I. Johannessen, $Ilo E. Leppik, ∗∗Torbj ¨orn Tomson,

and ††Emilio Perucca

∗Institute of Neurology/The National Hospital for Neurology and Neurosurgery, London and The Chalfont Centre

for Epilepsy, Chalfont St Peter, United Kingdom; †Medical Toxicology Unit, Guys and St. Thomas’ Hospital, London,

United Kingdom; ‡Harvard Medical School, Children’s Hospital Boston, Boston, Massachusetts, U.S.A.; §Center for

Orphan Drug Research, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, U.S.A.; ¶Children’s

Hospital Medical Center, Department of Neurology, Cincinnati, Ohio, U.S.A.; #The National Center for Epilepsy,

Sandvika, Division of Clinical Neuroscience, Rikshospitalet University Hospital, Oslo, Norway; $University of

Minnesota, Minneapolis, Minnesota, U.S.A.; ∗∗Karolinska University Hospital, Stockholm, Sweden; and ††Institute

of Neurology, IRCCS C. Mondino Foundation and Clinical Pharmacology Unit, University of Pavia, Pavia, Italy

SUMMARY

Although no randomized studies have demonstrated

a positive impact of therapeutic drug monitoring

(TDM) on clinical outcome in epilepsy, evidence

from nonrandomized studies and everyday

clinical experience does indicate that measuring

serum concentrations of old and new generation

antiepileptic drugs (AEDs) can have a valuable role

in guiding patient management provided that concentrations

are measured with a clear indication

and are interpreted critically, taking into account

the whole clinical context. Situations in which AED

measurements are most likely to be of benefit include

(1) when a person has attained the desired

clinical outcome, to establish an individual therapeutic

concentration which can be used at subsequent

times to assess potential causes for a change

in drug response; (2) as an aid in the diagnosis

of clinical toxicity; (3) to assess compliance, particularly

in patients with uncontrolled seizures or

breakthrough seizures; (4) to guide dosage adjustment

in situations associated with increased pharmacokinetic

variability (e.g., children, the elderly,

patients with associated diseases, drug formulation

changes); (5) when a potentially important pharmacokinetic

change is anticipated (e.g., in pregnancy,

or when an interacting drug is added or removed);

(6) to guide dose adjustments for AEDs

with dose-dependent pharmacokinetics, particularly

phenytoin.

KEYWORDS: Children, Elderly, Pregnancy, Drug

compliance, Saliva, Pharmacokinetics.

Background and historical introduction

Since drug action depends on the availability of the active

principle at receptor sites, knowledge of the pharmacokinetic

properties of the medication used is impor-

Accepted January 28, 2008; Online Early publication April 4, 2008.

Address correspondence to Professor Philip N. Patsalos, Chalfont Centre

for Epilepsy, Pharmacology and Therapeutics Unit, Chesham Lane,

Buckinghamshire, SL9 0RJ, U.K. E-mail: P.Patsalos@ion.ucl.ac.uk

Wiley Periodicals, Inc.

C  2008 International League Against Epilepsy

tant for optimal treatment. The treatment of epilepsy was

one of the first areas to benefit from pharmacokinetic

studies.

Both physicians

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