Intestinal expression of cytochrome P450 enzymes and ABC transporters and carbamazepine and phenytoin disposition.
Acta Neurol Scand
; 115(4): 232-42, 2007 Apr.
Article
en En
| MEDLINE
| ID: mdl-17376120
ABSTRACT
OBJECTIVES:
Interindividual variability in intestinal absorption and bioavailability might contribute to inadequate control of seizures under treatment with carbamazepine and phenytoin. We therefore correlated intestinal expression levels and genetics of CYP3A4, CYP2C9/19, MDR1 and MRP2 with dose requirement and plasma levels of carbamazepine and phenytoin. MATERIALS ANDMETHODS:
Epileptic patients on carbamazepine (n = 29) or phenytoin (n = 15) were stratified into a 'high'-dose (carbamazepine > or =800 mg/day, phenytoin > or =300 mg/day) and a 'low'-dose group (carbamazepine < or =600 mg/day, phenytoin < or =200 mg/day). Duodenal biopsies and DNA were obtained for Western blotting and genotyping studies.RESULTS:
Low carbamazepine plasma levels showed a trend towards higher intestinal MDR1 expression (P = 0.06). Furthermore, carbamazepine dose was positively correlated with MRP2 expression (P = 0.1). Moreover, MDR1 expression and carbamazepine and phenytoin dose requirement was influenced by the genotype in position 2677 and 3435 of the MDR1 gene.CONCLUSION:
Differences in intestinal MDR1 and MRP2 expression may influence carbamazepine and phenytoin disposition and may account for interindividual pharmacokinetic variability.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenitoína
/
Carbamazepina
/
Transportadoras de Casetes de Unión a ATP
/
Sistema Enzimático del Citocromo P-450
/
Duodeno
/
Anticonvulsivantes
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Acta Neurol Scand
Año:
2007
Tipo del documento:
Article
País de afiliación:
Suiza