Population pharmacokinetic modelling of carbamazepine by using the iterative Bayesian (IT2B) and the nonparametric EM (NPEM) algorithms: implications for dosage.

OBJECTIVE: To estimate individual and population postinduction pharmacokinetics of carbamazepine (CBZ) in epileptic adult and paediatric patients who received chronic CBZ monotherapy. METHODS: We have used the USC*PACK collection of PC programs for the estimations. The preinduction CBZ metabolism wa...

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Detalles Bibliográficos
Publicado en:Journal of Clinical Pharmacy & Therapeutics Vol. 26; no. 3; pp. 213 - 224
Autores principales: Bondareva IB, Sokolov AV, Tischenkova IF, Jelliffe RW
Formato: research tables/charts Journal Article
Publicado: Wiley-Blackwell 6/15/2001
Acceso en línea:Ver este registro en EBSCOhost
Descripción
Sumario:OBJECTIVE: To estimate individual and population postinduction pharmacokinetics of carbamazepine (CBZ) in epileptic adult and paediatric patients who received chronic CBZ monotherapy. METHODS: We have used the USC*PACK collection of PC programs for the estimations. The preinduction CBZ metabolism was also estimated in 16 volunteers after a single dose of CBZ (200 mg). We used a linear one-compartmental model with oral absorption and found the pharmacokinetic parameter values of CBZ behaviour to be in good agreement with those reported earlier. RESULTS: Serum CBZ concentrations correlated poorly with daily doses in both the adult and child populations. Because of the diversity within the population, use of the mean population model without knowledge of an individual patient's pharmacokinetic characteristics gives poor prediction. In contrast, the individual Bayesian posterior models gave good prediction for all subjects in the population, due to the removal of the interindividual variability. CONCLUSION: This approach permits one to individualize drug therapy for patients even when only sparse therapeutic drug monitoring (TDM) data are available. Future individual CBZ serum level predictions were acceptable from a clinical point of view (mean absolute error = 13.2 +/- 9.7%). The optimal sampling strategy approach helped to design an optimal cost-effective TDM protocol for CBZ therapy management.