Relationship between lamotrigine oral dose, serum level and its inhibitory effect on CNS: insights from transcranial magnetic stimulation.
Epilepsy Res
; 56(1): 67-77, 2003 Sep.
Article
en En
| MEDLINE
| ID: mdl-14529954
ABSTRACT
The antiepileptic drug lamotrigine (LTG) is known to reduce cortical excitability evaluated by transcranial magnetic stimulation (TMS). We investigated the relationship between LTG oral dosages, serum levels and inhibitory effects on resting motor threshold (RMT), a parameter of motor system excitability assessed by TMS. In a randomized, placebo-controlled crossover study 16 male volunteers received 325 mg LTG as a single dose, as bi-hourly graded cumulative dose, or placebo. RMT and serum levels were measured before and after 2-8 h. With single dose, RMT elevation showed a poor but significant correlation to serum levels. With graded dose, serum levels as well as RMT increased dose-dependently with significant (P<0.0001) linear correlation. However, detailed comparison showed a high inter-individual variability in the relationship resembling a sigmoid correlation. Different mechanisms besides the sodium-channel blockage as the main mode of action of LTG are discussed to explain the diversity of individual dose-response relationships. Provided that the RMT elevation reflects the antiepileptic potential of LTG, TMS may be developed as a tool to monitor interindividual response of epilepsy patients to LTG treatment as well as to explore efficacy of other antiepileptic drugs with similar mode of action.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Triazinas
/
Sistema Nervioso Central
/
Estimulación Magnética Transcraneal
/
Anticonvulsivantes
/
Inhibición Neural
Tipo de estudio:
Clinical_trials
/
Diagnostic_studies
Límite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Epilepsy Res
Asunto de la revista:
CEREBRO
/
NEUROLOGIA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS