Effects of Age, Sex, and Comedication on the Plasma Concentrations of Olanzapine in Chinese Patients With Schizophrenia Based on Therapeutic Drug Monitoring Data

作者：Jing Ding, Yan Zhang, Yan Zhang, Jing Yang, Suo Zhang, Xiaohua Cui, Zhuocheng Meng, Yajuan Li, Huan Xing · 发表于：Journal of Clinical Psychopharmacology · 年份：2022 · DOI：10.1097/jcp.0000000000001618 · 被引用次数：7 · 研究领域：Schizophrenia research and treatment、Bipolar Disorder and Treatment、Treatment of Major Depression

BACKGROUND: Olanzapine (OLA) is an atypical second-generation antipsychotic that exhibits significant pharmacokinetic variability. We retrospectively investigated the effects of age, sex, and specific comedications on OLA pharmacokinetics in Chinese patients with schizophrenia. METHODS: Data on sex, age, and OLA dosage and steady-state plasma concentrations of 386 patients with schizophrenia (who have received OLA or a comedication of OLA with a psychotherapeutic drug) were collected and analyzed. The combined effects of dosage, age, sex, and comedication on OLA plasma levels were assessed via multiple linear regression analyses. RESULTS: A daily dose of OLA was positively correlated with the drug's plasma concentrations. Overall, the OLA plasma concentrations and concentration-to-dose ratio (C/D) of the studied patients varied by 53.6- and 64.1-fold, achieving median values of 42.7 ng/mL and 2.73 (ng/mL)/(mg/d), respectively. Furthermore, a 1.27-fold higher estimated C/D in patients 60 years or older than in those younger than 60 years was identified. Female patients demonstrated a 33.6% higher C/D than in male patients. When coadministered with mood stabilizers (valproate or lithium), the median OLA C/D was 24.1% to 26.1% lower than that of OLA monotherapy. Interestingly, the OLA plasma concentration and C/D were not significantly affected by a comedication with aripiprazole, haloperidol, amisulpride, risperidone, clozapine, ziprasidone, citalopram, or buspirone. CONCLUSION...