Terapéutico medicinal supervisión sobre el tratamiento de la epilepsia
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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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