|Population pharmacokinetics modeling of levetiracetam in Chinese children with epilepsy|
|Wang, Ying-hui1; Wang, Li1; Lu, Wei2; Shang, De-wei2; Wei, Min-ji1; Wu, Ye1|
|关键词||Levetiracetam Epilepsy Population Pharmacokinetics Pediatric Chinese Children|
|刊名||ACTA PHARMACOLOGICA SINICA|
|WOS标题词||Science & Technology|
|类目[WOS]||Chemistry, Multidisciplinary ; Pharmacology & Pharmacy|
|研究领域[WOS]||Chemistry ; Pharmacology & Pharmacy|
|关键词[WOS]||REFRACTORY PARTIAL SEIZURES ; ADD-ON THERAPY ; HPLC-UV ; VALPROATE ; PLASMA ; DRUGS|
Aim: 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 V/F=12.1 (L), CL/F=1.04x(WEIG/25)(0.563)(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).
Conclusion: 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.
|资助机构||UCB Pharma (Braine-l&prime ; Alleud, Belgium) ; Capital Development Fund of Medical Research of China|
|作者单位||1.Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China|
2.Peking Univ, Dept Pharmaceut, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
|Wang, Ying-hui,Wang, Li,Lu, Wei,et al. Population pharmacokinetics modeling of levetiracetam in Chinese children with epilepsy[J]. ACTA PHARMACOLOGICA SINICA,2012,33(6):845-851.|
|APA||Wang, Ying-hui,Wang, Li,Lu, Wei,Shang, De-wei,Wei, Min-ji,&Wu, Ye.(2012).Population pharmacokinetics modeling of levetiracetam in Chinese children with epilepsy.ACTA PHARMACOLOGICA SINICA,33(6),845-851.|
|MLA||Wang, Ying-hui,et al."Population pharmacokinetics modeling of levetiracetam in Chinese children with epilepsy".ACTA PHARMACOLOGICA SINICA 33.6(2012):845-851.|