Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Prediction of steady-state plasma concentrations of olanzapine in Chinese Han in patients based on a retrospective population pharmacokinetic model

Xiaoyue Wang¹, Yong Han², Hong Zhou², Bin Cao³, Miaomiao Zhu¹, Chunfang Liu¹, Chao Gao¹, Howard L McLeod⁴, Maosheng Fang¹

¹Department of Pharmacy, Wuhan Mental Health Center, Wuhan, China; ²Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; ³Department of Information, Wuhan Mental Health Center, Wuhan, China; ⁴Taneja College of Pharmacy and the Geriatric Oncology Consortium, University of South Florida, Tampa FL 33618, USA.

For correspondence:- Maosheng Fang Email: fangmaosheng2006@163.com Tel:+862785869112

Accepted: 19 October 2021 Published: 30 November 2021

Citation: Wang X, Han Y, Zhou H, Cao B, Zhu M, Liu C, et al. Prediction of steady-state plasma concentrations of olanzapine in Chinese Han in patients based on a retrospective population pharmacokinetic model. Trop J Pharm Res 2021; 20(11):2433-2441 doi: 10.4314/tjpr.v20i11.28

© 2021 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To develop robust methods of establishing a population pharmacokinetics (Pop-PK) model of olanzapine, using existing hospital in-patient information, in order to predict the steady-state plasma concentration of olanzapine tablets in Chinese Han inpatients, thus providing guidance for individualized therapy for mental disorders.

Methods: A retrospective study analyzing and predicting the steady-state plasma olanzapine concentration was performed using nonlinear mixed-effect modeling (Phoenix® NLME8). The effects of ten potential covariates, including age, gender, Body Mass Index, fasting lipid, family history, alcohol and smoking status in 107 Chinese Han patients with steady-state plasma olanzapine concentration were collected from the hospital information system (HIS) in Wuhan Mental Health Center from Feb 2017 to Jul 2019.

Results: The final model was validated using bootstrap and visual predictive check (VPC) and was found to fit the one-compartment mixed error model. Smoking status was found to be the only factor affecting olanzapine tablets clearance. The standard Pop-PK parameters apparent volume of distribution (VL/F) and clearance (CL/F) were 223 L and 12.4 L·h-1, respectively.

Conclusion: The Pop-PK model for olanzapine established with the data from HIS is effective in predicting the plasma olanzapine tablets concentration of individual Chinese in-patients. This Pop-PK model approach can now be adapted to optimize other antipsychotic drugs.

Keywords: Population pharmacokinetics, Plasma, Steady-state, Olanzapine, Retrospective model, Chinese Han