In vitro cytochrome p450 activity decreases in children with high pediatric end-stage liver disease scores.
Drug Metab Dispos
; 41(2): 390-7, 2013 Feb.
Article
en En
| MEDLINE
| ID: mdl-23150427
To improve the modeling and simulation of pharmacokinetics in pediatric patients, research into developmental and disease-specific determinants is needed. This article describes the evaluation of the activity of in vitro cytochrome P450 (P450), an important enzyme family in drug metabolism, in children with hepatic dysfunction. The activity of six P450 isoforms (CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4) was evaluated in 31 patients with different pathologies, predominantly biliary atresia (n = 23). Hypervariable activity was observed for all the isoforms. Compared with average adult activity, low activity levels were seen for CYP1A2, 2C19, 2E1, and 3A4. For CYP2E1 and 3A4, a positive correlation between activity and abundance was observed. Age, comedication, and genotype could not be used as predictors for P450 activity in this patient population. In contrast, the pediatric end-stage liver disease score was negatively correlated with the ln(activity). This finding suggests a decrease in P450 activity with deteriorating hepatic function. Moreover, the activity of all isoforms was correlated, demonstrating a concomitant decrease of all isoforms in young patients with liver disease. To our knowledge, this is the first study to evaluate P450 activity in children with hepatic impairment. The presented data may provide support in the further optimization of a disease-specific model in this patient population.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sistema Enzimático del Citocromo P-450
/
Enfermedad Hepática en Estado Terminal
/
Hígado
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Aspecto:
Patient_preference
Límite:
Child
/
Child, preschool
/
Humans
/
Infant
/
Newborn
Idioma:
En
Revista:
Drug Metab Dispos
Asunto de la revista:
FARMACOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Bélgica
Pais de publicación:
Estados Unidos