Population pharmacokinetic meta-analysis method was used in order to obtain the pharmacokinetic characteristics of risperidone and its active metabolite. Eighteen studies were selected from published papers from 1995 to 2011. A model consisted of two compartments for parent drug and one compartment for its active metabolite combined with a flexible absorption process was developed based on the meta-dataset. The population-predicted apparent clearance for risperidone and 9-hydroxyrisperidone, the active metabolite was 7.66 L/h and 7.38 L/h, and the apparent volume of distribution in the central compartment was 70.6 L and 117 L, respectively. The final model was evaluated by visual predictive check（VPC） based on 1000 times model simulation. This model was adequately used to predict clinical therapeutic drug monitoring（TDM） data from 42 Chinese inpatients. Bias（mean prediction errors, MPE） and precision（root mean squared prediction errors, RMSE） were calculated to statistically analysis the population prediction error. It was demonstrated that the model developed from the meta-dataset was reliable and can be used to facilitate the individualized treatment for a target population.
A tablet consisting of direct-acting antiviral agents,ledipasvir（a NS5 A protein inhibitor） and sofosbuvir（a NS5 B polymerase inhibitor）,is the first fixed-dose preparation used in the antiviral therapy of hepatitis C.A model-based meta-analysis of ledipasvir and GS331007,the primary metabolite of sofosbuvir,enabled the integration of pharmacokinetic（PK） information from separate clinical trials and the quantitative characterization of the population pharmacokinetics of these two drugs.A systematic publication search was conducted for the clinical studies of ledipasvir and sofosbuvir.A total of 401 arm-level aggregate concentrations of GS331007 and 188 concentrations of ledipasvir were used for PK modeling.A two-compartment disposition model was used for both ledipasvir and GS331007.Zero-order absorption was applied for ledipasvir PK modeling,and a combined zero- and first-order absorption was used for the modeling of GS331007.Absorption lag was observed in concentration-time profiles of both ledipasvir and GS331007.To aid the development of direct-acting antiviral drugs,our established PK models provided a basis for the further PK-viral kinetic studies of ledipasvir and sofosbuvir.
