Population pharmacokinetics analysis of olanzapine for Chinese psychotic patients based on clinical therapeutic drug monitoring data with assistance of meta-analysis.
OBJECTIVE
The aim of this study was to build an eligible population pharmacokinetic (PK) model for olanzapine in Chinese psychotic patients based on therapeutic drug monitoring (TDM) data, with assistance of meta-analysis, to facilitate individualized therapy.


METHODS
Population PK analysis for olanzapine was performed using NONMEM software (version 7.3.0). TDM data were collected from Guangzhou Brain Hospital (China). Because of the limitations of TDM data, model-based meta-analysis was performed to construct a structural model to assist the modeling of TDM data as prior estimates. After analyzing related covariates, a simulation was performed to predict concentrations for different types of patients under common dose regimens.


RESULTS
A two-compartment model with first-order absorption and elimination was developed for olanzapine oral tablets, based on 23 articles with 390 data points. The model was then applied to the TDM data. Gender and smoking habits were found to be significant covariates that influence the clearance of olanzapine. To achieve a blood concentration of 20 ng/mL (the lower boundary of the recommended therapeutic range), simulation results indicated that the dose regimen of olanzapine should be 5 mg BID (twice a day), ≥ 5 mg QD (every day) plus 10 mg QN (every night), or >10 mg BID for female nonsmokers, male nonsmokers and male smokers, respectively.


CONCLUSIONS
The population PK model, built using meta-analysis, could facilitate the modeling of TDM data collected from Chinese psychotic patients. The factors that significantly influence olanzapine disposition were determined and the final model could be used for individualized treatment.
School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.|Peking University/Pfizer Pharmacometrics Education Center, Peking University Health Science Center, Beijing, 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.
Anyue
A
Yin
Guangzhou Brain Hospital (Guangzhou Huiai Hospital, the Affiliated Brain Hospital of Guangzhou Medical University), Guangzhou, 510370, China.
Dewei
D
Shang
Guangzhou Brain Hospital (Guangzhou Huiai Hospital, the Affiliated Brain Hospital of Guangzhou Medical University), Guangzhou, 510370, China.
Yuguan
Y
Wen
School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.|Peking University/Pfizer Pharmacometrics Education Center, Peking University Health Science Center, Beijing, 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.
Liang
L
Li
School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.|Peking University/Pfizer Pharmacometrics Education Center, Peking University Health Science Center, Beijing, 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.
Tianyan
T
Zhou
School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. luwei_pk@bjmu.edu.cn.|Peking University/Pfizer Pharmacometrics Education Center, Peking University Health Science Center, Beijing, 100191, China. luwei_pk@bjmu.edu.cn.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China. luwei_pk@bjmu.edu.cn.|Beijing Institute for Brain Disorders, Beijing, 100088, China. luwei_pk@bjmu.edu.cn.
Wei
W
Lu
D000284:Administration, Oral; D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044466:Asian People; D001569:Benzodiazepines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D000077152:Olanzapine; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D012907:Smoking / Q000097:blood / Q000378:metabolism; D055815:Young Adult
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine
Model-based meta-analysis; Olanzapine; Population pharmacokinetic model; Psychotic; Therapeutic drug monitoring