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.