A Retrospective Analysis of Steady-State Olanzapine Concentrations in Chinese Patients Using Therapeutic Drug Monitoring: Effects of Valproate and Other Factors

Abstract

Background: The objective of this study was to investigate the serum concentrations of olanzapine in relation to age, sex, and other factors in Chinese patients aged between 10 and 90 years. Methods: Data for 884 olanzapine patients, deposited between 2016 and 2017, were retrieved from the therapeutic drug monitoring database of the Affiliated Brain Hospital of Guangzhou Medical University. The effects of covariates on serum olanzapine concentration, dose-normalized concentration (C/D ratio), and normalized concentration (C/D/weight) were investigated. Results: Generally, male patients had lower olanzapine concentration, C/D ratio, and C/D/weight than female patients (P < 0.001). Smoking and drinking reduced olanzapine concentration, C/D ratio, and C/D/weight (P < 0.001). Coadministration with valproate decreased olanzapine concentration, C/D ratio, and C/D/weight by about 16%, 30%, and 40%, respectively (P < 0.001). Patients younger than 60 years had higher olanzapine concentrations (P < 0.05) but lower C/D ratios and C/D/weight (P < 0.001) than patients older than 60 years. Age was correlated with olanzapine concentration (r = −0.082, P < 0.05), C/D ratio (r = 0.196, P < 0.001), and C/D/weight (r = 0.169, P < 0.001). Sample timing after dose and diagnostic factors also contributed to the olanzapine concentrations. Multiple linear regression analysis revealed significant influences of dosage, age, sex, valproate comedication, smoking, postdose interval, and schizophrenia (vs bipolar affective disorders) on serum olanzapine concentrations. Conclusions: The metabolism of olanzapine may be altered by several factors. Patients characterized with a combination of factors may benefit from therapeutic drug monitoring for the adjustment of olanzapine dose to minimize adverse reactions.

Effects of Age, Drug Dose, and Sampling Time on Salivary Levels of Olanzapine, Quetiapine, and Their Metabolites

“…A comparison of saliva olanzapine levels collected 15 min before and 2 h after application of the drug show a considerable and statistically significant difference which was not observed for its metabolite, N-demethyl olanzapine. This observation is in line with literature data, which indicate the significance of time elapsed from the application of the drug to the collection of samples for the determined blood drug levels [ 7 ].…”

“…Raw levels of its metabolite, N-demethyl olanzapine, were also lower in women. However, literature data show that their blood levels are higher in women than in men [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 14 , 15 ], which may be associated with a certain limitation of our study, where the group starting the treatment consisted solely of women, and the group of long-time users was predominantly male.…”

“…Research on the relationship between drug levels in the body and the dose, weight, age, or levels of additional drugs in the system is usually conducted in the blood. It has been shown that in women, as well as in people over 60 years of age, the concentration of olanzapine in the blood is higher than in men and younger people [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. It was also noted that in smokers, the metabolism of olanzapine is faster and the drug concentration is lower than in non-smokers [ 3 , 4 , 6 , 7 , 10 , 11 ].…”

“…It has been shown that in women, as well as in people over 60 years of age, the concentration of olanzapine in the blood is higher than in men and younger people [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. It was also noted that in smokers, the metabolism of olanzapine is faster and the drug concentration is lower than in non-smokers [ 3 , 4 , 6 , 7 , 10 , 11 ]. Moreover, olanzapine shows very high variability of its concentration in blood, reaching as much as 47% [ 3 , 12 ], which was found when serum samples were collected multiple times (up to 24) from the same person, treated with the same dose, over a period of several months.…”

Therapeutic Drug Monitoring of Second- and Third-Generation Antipsychotic Drugs—Influence of Smoking Behavior and Inflammation on Pharmacokinetics

“…Since the polycyclic aromatic hydrocarbons in tobacco smoke mainly affect CYP1A2, most data on smoking behavior and changes in plasma concentration pertain to SGAs such as clozapine and olanzapine, which are CYP1A2 substrates. In general, smokers have lower serum levels of clozapine and olanzapine than non-smokers when treated with the same oral dose [33,67,[213][214][215][216][217][218][219]. Published reports document 20-40% lower mean serum clozapine concentrations in smokers (up to 14 cigarettes per day) compared with nonsmokers due to enzyme induction [67].…”