PHARMACOLOGY RESEARCH IN PEDIATRIC NEUROLOGY
Wang L, Zuo C-H
Pediatric Neurology, Beking University First
Hospital, Beijing, China
Objective: To study
comprehensively the scientific therapy and the related mechanisms of
antiepileptic drugs (AEDs) in both clinic and laboratory.
Methods: Developing the
epilepsy models including kindling and new; developing the methods
determining blood levels of AEDs; exploring pharmacokinetics /
pharmacodynemics (PK/PD), tolerance/dependence, drug interactions, effects
on brain development and cognitive, new AEDs, Chinese traditional AED and
their related mechanisms.
Results: 1. Successful introduce the therapeutic drug
monitoring (TDM); established the effective/toxic blood levels,
dosage/concentration/effect relationship; increase the complete control
rate from 40% before TDM to 80% after TDM; extend the using of
loading dose for emergency seizures of newborn. 2.
Revealed the olerance / dependence to antiseizure is functional but
pharmacokinetic; GABAA receptors and subunits are down-regulation while
tolerance and up-regulation while dependence. 3. Clinical trail by
double-blind, crossover-controlled suggest Chinese new AES is promising;
data in two kind of kindling rats verified the antiseizure effects are seizure
type dependent. 4. Cognitive effects of 8 conventional AEDs are different,
related to blood levels, type and onset age; LTP and the c-fos repression
are valuable markers; AEDs choice should depend on both anti-seizure and
cognitive effect. 5. Interactions study by PQEEG, biochemistry and
electromacroscope revealed developing PK/PD model can be used in clinic; PB
and 7903 significantly decreased CZP blood levels,
T1/2, AUC, Cmax, increased Ke, Cl, by induced P450ase
content and numbers of smooth endoplasmic reticulum. VPA and Erythromycin
were on the contrary.
Conclusion: Good subject should
come from clinic, creative research results must serve for clinic.
Pharmacology studies combing clinic with basic are important to drug
therapy in pediatric neurology.