PDF File - Mahidol University

380
Abstracts
MS-10
Therapeutic Drug Monitoring
MS-10-1
Therapeutic drug monitoring (TDM) of anti-epileptic
drugs in children
P. Walson
Professor of Pediatrics, University of Cincinnati Director,
Division of Clinical Pharmacology and Clinical Trials
Office Children’s Hospital Medical Center, USA
Accurate measurement and proper interpretation of drug
concentrations (TDM) can greatly improve medical diagnosis
and management. However, TDM requires much more
than just measurement of drug concentrations. TDM is a
process by which measurement of drug concentrations is
combined with knowledge of the drug’s pharmacokinetics
and pharmacodynamics, as well as with patient specific
analytical and clinical data. TDM is useful for all drugs in
some specific clinical situations. TDM is especially useful
for drugs with: (a) a well-defined relationship between
concentration and effects (either therapeutic or toxic); (b)
wide inter- or intra-individual differences in drug clearance;
and (c) where this is no readily available method to clinically
assess therapeutic or toxic effects. Antiepileptic drugs
(AEDs) are examples of drugs for which properly done
TDM has been shown to improve efficacy while decreasing
toxicity. A number of published studies done over the past
20 years in our laboratory with older AEDs will be briefly
reviewed. Some important general and specific principles of
pediatric TDM will be discussed including some practical
and theoretical differences between children and adults.
Some examples will be discussed to illustrate how proper
pediatric TDM differs from ‘numbers only’ reporting of
concentrations. These studies illustrate how much can be
learned about pediatric AED use from a review of properly
collected, analyzed and interpreted AED TDM database.
These data also demonstrate the wide intra-individual differences
in AED clearance and illustrate why TDM is required
to effectively individualize AED dosing to treat pediatric
seizure patients. Finally, data on the usefulness of TDM
of newer AEDs will be discussed.
MS-10-2
Developmental and therapeutic pharmacology of
antiepileptic drugs
H. Miura
Department of Pediatrics, Kitasato University School of
Medicine, Sagamihara, Kanagawa, Japan
We investigated the clinical effects and plasma levels of
zonisamide (ZNS) in children with cryptogenic localizationrelated
epilepsies. ZNS is absorbed slowly and its biological
half-life is long as compared with that of other antiepilepic
drugs. The peak-to-trough plasma level ratios during a day
were as small as 1.28 ^ 0.15 in children taking a daily dose of
8 mg/kg of ZNS once a day as a single drug. The plasma level
(mg/ml) to dose (mg/kg per day) ratios estimated by the
trough and peak plasma levels both increased with advancing
age, but the peak-to-trough plasma level ratios were maintained
almost uniformly throughout the pediatric age period.
A wide range of the plasma levels was associated with
complete freedom from seizures. However, the clinical
effects of ZNS were in agreement with the range of generally
accepted therapeutic plasma levels of 15–40 mg/ml. Any
patient who receives polytherapy is at risk to develop drug
interactions. Concurrent administration of carbamazepine
(CBZ) decreases plasma concentrations of ZNS. However,
ZNS does not alter plasma concentrations of CBZ or its
primary metabolite, carbamazepine-10,11-epoxide (CBZ-
E). Drug-protein binding interactions are one source of side
effects. A simultaneous administration of valproic acid
increases the total plasma CBZ-E levels relative to the
CBZ dose associated with the raised free fractions of CBZ
and CBZ-E. The free plasma concentrations of CBZ-E above
1.5 mg/ml may be responsible for the side effects.
WORKSHOP
WS-1
Cerebral Palsy
WS-1-1
Etiology and risk factors for cerebral palsy
V. Kalra
Department of Pediatrics, All India Institute of Medial
Sciences, Ansari Nagar, New Delhi, India
Cerebral palsy (CP) implies a group of non-progressive
neuromotor impairment syndromes due to an acute insult to
the developing brain. Prenatal and perinatal period provides
greatest vulnerability. The casual factors are complex, often
multiple and the attributable risk from an individual factor is
often difficult to define in a patient. Preterm, extreme low
birth weight, multiple pregnancies, perinatal hypoxia, hypoglycemia,
hypothermia, sepsis and jaundice remain
commonly identifiable perinatal factors in our data. In
developing countries with domiciliary deliveries, perinatal
hypoxia still remains an important contributory factor.
Prevention of perinatal hypoxia neonatal sepsis, hypothermia
hypoglycemia are important in developing countries.
Congenital intrauterine infections are important identifiable
factors due to therapy issues. Malformations of the brain
remain an important cause to identify. Maternal infections
are assuming greater importance. Maternal socioeconomic
status, anemia, systemic diseases, hypertension, iodine deficiencies
unattended during pregnancy are not uncommon in
developing countries. Neuroinfections and acquired neurological
insults in early childhood are also more frequent than
in developing countries. Risk factors for CP in developing