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 olanzapineconcentration 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 Lꞏh-1, respectively.Conclusion: The Pop-PK model for olanzapine established with the data from HIS is effective inpredicting the plasma olanzapine tablets concentration of individual Chinese in-patients. This Pop-PK model approach can now be adapted to optimize other antipsychotic drugs.
Highlights
A mental disorder is a behavioral or mental pattern that is caused by the dysfunctioning of the central nervous system, and it results in significant distress or impairment of personal functioning [1]
The population pharmacokinetics (Pop-PK) model was aptly used to examine the effect of plasma concentration on olanzapine clearance, and to predict steady-state plasma olanzapine concentration of inpatients, which is consistent with previous reports [14]
The findings demonstrated that prediction of plasma olanzapine tablets concentration using the same Pop-PK model is feasible, which is consistent with the study by Tsuboi et al [21]
Summary
A mental disorder is a behavioral or mental pattern that is caused by the dysfunctioning of the central nervous system, and it results in significant distress or impairment of personal functioning [1]. It is estimated that there are approximately 1 billion people with mental disorders worldwide, and more than 240 million of these patients are in China [2]. -©---2-0--2--1---T--h-e---a--u-t-h--o-r-s--.--T-h--i-s--w--o--r-k--i-s--l-i-c-e--n-s--e--d--u--n-d--e--r--th--e---C--r-e-a--t-i-v-e---TC--ro-om-p--m-J-o-P-n-h-s-a-A-r-mt-t-r-iR-b-ue--st-i,o--Nn--o-4-v.-0e--m-In-b-t-ee-r-r-n2-a-0-t-2io-1-n-;-a-2l--0L-(-ic1--e1-n-)-:s--e2-4--3--3 novel therapy, and the second most commonly used atypical antipsychotic drug (13.1% of prescriptions) for the treatment of mental disorders in China [3]. Olanzapine has demonstrated efficacy in ameliorating both the negative and positive symptoms of schizophrenia. Patients receiving olanzapine treatment have shown fewer extrapyramidal adverse effects than those receiving firstgeneration antipsychotics (FGA) [4]. Olanzapine can often result in assorted adverse drug reactions (ADRs), such as cardiovascular disease, lipid metabolism disorder, diabetes mellitus, motor side effects, and weight gain, and the severity of these ADRs is dose-dependent [5]. The clinical efficacy of olanzapine was previously shown to be influenced by its plasma concentration [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
