Population pharmacokinetics of valproate in Chinese children with epilepsy

Abstract

Aim: The aim of the present study is to establish a population pharmacokinetic (PPK) model of valproate (VPA) in Chinese epileptic children to promote the reasonable use of anti-epileptic drugs. Methods: Sparse data of VPA serum concentrations from 417 epileptic children were collected. These patients were divided into 2 groups: the PPK model group (n=317) and the PPK valid group (n=100). The PPK parameter values of VPA were calculated by NONMEM software using the data of the PPK model group. A basic model and a final model were set up. To validate the 2 models, the concentrations of PPK valid group were predicted by each model, respectively. The mean prediction error (MPE), mean squared prediction error (MSPE), root mean squared prediction error (RMSPE), weight residues (WRES), and the 95% confidence intervals (95% CI) were also calculated. Then, the values between the 2 models were compared. Results: The PPK of VPA was determined by a 1-compartment model with a first-order absorption process. The basic model was: Ka=3.09 (h (-30.36, -16.70), 3728.96 (2872.72, 4585.20), 39.62 (34.34, 44.90), and -0.06 (-0.14, 0.02), respectively. For the final model, the MPE, MSPE, RMSPE, WRES, and the 95% CI were -1.16 (-4.85, 2.53), 1002.83 (1050.64, 1143.61), 23.04 (21.12, 24.96), and 0.08 (-0.04, 0.20), respectively. The final model was more optimal than the basic model. Conclusion: The PPK model of VPA in Chinese epileptic children was successfully established. It will be valuable to facilitate individualized dosage regimens. Key wordspopulation pharmacokinetics; valproic acid; epi l epsy; chi l dr en; B a yesi an met hod; NONMEM software; individualized dosage regimens

A systematic review of population pharmacokinetics of valproic acid

“…Table summarizes the characteristics of each study. Most of the models were developed in patients with epilepsy . One study reported a model incorporating data from both epileptic and psychiatric patients .…”

Population pharmacokinetics modeling of levetiracetam in Chinese children with epilepsy

“…To assess the accuracy and precision of the concentration prediction, the mean prediction error (MPE), mean squared prediction error (MSPE), root mean-squared prediction error (RMSPE), weight residues (WRES), and the 95% confidence intervals (95% CI) were calculated. Then, the values of the two models were compared [19] . The shrinkage for each of the parameters in the model was evaluated using the method described by Karlsson [20] .…”

In‐situ Apparent Mobility of Charge Carriers in Polyaniline Films Measured with a New Four‐band Electrode

“…Therefore the variation of the apparent mobility will provide information to facilitate the study of the conduction mechanism. However, up to now all the measurements of apparent mobilities by the above electrochemical technique are carried out with two-band electrodes, [6][7][8]13 which is difficult to eliminate the influence of contact resistance. In our insight, four-probe method has not been applied in this new electrochemical technique to measure in-situ apparent mobility.…”

“…In recent years, an electrochemical technique on the basis of two-probe method was successfully developed to measure the in-situ mobility under different doping potentials. [6][7][8]13 Thus measured mobilities are apparent mobilities since the evaluation is based on a single-carrier model. The apparent mobility of charge carriers in a polymer film will vary if the sort of charge carriers changes as the oxidation state of the polymer proceeds.…”