Determination of the Optimal Concentration of XXXX in @entity1 with @entity302 : A Population Pharmacokinetic-Pharmacodynamic Analysis.

@entity1 @entity410 @entity3262 @entity1092 @entity39505 @entity1372 @entity1771 @entity302 @entity3174 @entity2049 @entity2053
UNASSIGNED: @entity1092 ( @entity3262 ) is one of the most widely prescribed antiepileptic drugs for the treatment of @entity302 . Although it is well known that the doses of @entity3262 and its plasma concentrations are highly correlated, the plasma concentrations do not correlate well with the therapeutic effects of the @entity3262 . In this study, we developed a population-based pharmacokinetic (PK)-pharmacodynamic (PD) model to determine the optimal concentration of @entity3262 according to the clinical characteristics of each @entity1 . This retrospective study included 77 @entity3262 -treated Japanese @entity1 with @entity302 . A nonlinear mixed-effects model best represented the relationship between the trough concentrations of @entity3262 at steady-state and an over 50% reduction in @entity410 frequency. The model was fitted using a logistic regression model, in which the logit function of the probability was a linear function of the predicted trough concentration of @entity3262 . The model showed that the age, @entity410 locus, the @entity1372 channel neuronal type I alpha subunit @entity39505 polymorphism and co-administration of @entity2049 , @entity2053 , @entity3174 or @entity1771 were associated with an over 50% reduction in the @entity410 frequency. We plotted the receiver operating characteristic (ROC) curve for the logit(Pr) value of the model and the presence or absence of a more than 50% reduction in @entity410 frequency, and the areas under the curves with the 95% confidence interval from the ROC curve were 0.823 with 0.793-0.853. A logit(Pr) value of 0.1 was considered the optimal cut-off point (sensitivity = 71.8% and specificity = 80.4%), and we calculated the optimal trough concentration of @entity3262 for each @entity1 . Such parameters may be useful to determine the recommended therapeutic concentration of @entity3262 for each @entity1 , and the procedure may contribute to the further development of personalized pharmacological therapy for @entity302 .
