Population pharmacokinetics modeling of levetiracetam in Chinese children with epilepsy.
OBJECTIVE
To establish a population pharmacokinetics (PPK) model of levetiracetam in Chinese children with epilepsy.


METHODS
A total of 418 samples from 361 epileptic children in Peking University First Hospital were analyzed. These patients were divided into two groups: the PPK model group (n=311) and the PPK validation group (n=50). Levetiracetam concentrations were determined by HPLC. The PPK model of levetiracetam was established using NONMEM, according to a one-compartment model with first-order absorption and elimination. To validate the model, 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.


RESULTS
A regression equation of the basic model of levetiracetam was obtained, with clearance (CL/F)=0.988 L/h, volume of distribution (V/F)=12.3 L, and K(a)=1.95 h(-1). The final model was as follows: K(a)=1.56 h(-1), V/F=12.1 (L), CL/F=1.04×(WEIG/25)(0.583) (L/h). For the basic model, the MPE, MSPE, RMSPE, WRES, and the 95%CI were 9.834 (-0.587-197.720), 50.919 (0.012-1286.429), 1.680 (0.021-34.184), and 0.0621 (-1.100-1.980). For the final model, the MPE, MSPE, RMSPE, WRES, and the 95% CI were 0.199 (-0.369-0.563), 0.002082 (0.00001-0.01054), 0.0293 (0.001-0.110), and 0.153 (-0.030-1.950).


CONCLUSIONS
A one-compartment model with first-order absorption adequately described the levetiracetam concentrations. Body weight was identified as a significant covariate for levetiracetam clearance in this study. This model will be valuable to facilitate individualized dosage regimens.
Pediatric Department of Peking University First Hospital, Beijing, China.
Ying-hui
YH
Wang
Li
L
Wang
Wei
W
Lu
De-wei
DW
Shang
Min-ji
MJ
Wei
Ye
Y
Wu
D000293:Adolescent; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D000077287:Levetiracetam; D008954:Models, Biological; D015233:Models, Statistical; D010889:Piracetam / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam