Zhang Cun, Chen Liang, Duan Yin-Yin, He Su-Mei, Tian Ya-Li, Gao Ying, Wang Dong-Dong
Department of Pharmacy, Xuzhou Oriental Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, China.
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy & School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Front Psychiatry. 2025 May 13;16:1538996. doi: 10.3389/fpsyt.2025.1538996. eCollection 2025.
Olanzapine is already used to treat patients with major depressive disorder; however, whether complex drug-drug interaction (DDI) has an effect on the pharmacokinetics of people using olanzapine and its initial dosage remains unknown. The present study aims to explore the effect of DDI on olanzapine.
In total, 72 patients with major depressive disorder were included for analysis. Potential physiological and biochemical indices and other drug combination information were collected to explore the effect of clinical olanzapine concentrations by building a nonlinear mixed effect (NONMEM) model and to further simulate the optimal olanzapine initial dosage by use of the Monte Carlo method in patients with major depressive disorder.
Weight and combined use of paroxetine significantly affected olanzapine clearance. With the same weight, the clearance rates of olanzapine were 0.711:1 in patients with major depressive disorder with or without paroxetine. For the initial dosages, without paroxetine, the olanzapine administration dosages, 0.5 and 0.4 mg/kg/day were recommended for patients with major depressive disorder in the groups weighing 40 to 56 kg and 56 to 100 kg, respectively. With paroxetine, olanzapine administration dosages of 0.3 and 0.2 mg/kg/day were recommended for patients with major depressive disorder in the groups weighing 40 to 85 kg and 85 to 100 kg, respectively.
This has been the first case to establish olanzapine population pharmacokinetics in patients with major depressive disorder. In addition, the present study innovatively clarified that paroxetine affected olanzapine population pharmacokinetics and initial dosage in patients with major depressive disorder.
奥氮平已用于治疗重度抑郁症患者；然而，复杂的药物相互作用（DDI）是否会对使用奥氮平患者的药代动力学及其初始剂量产生影响尚不清楚。本研究旨在探讨药物相互作用对奥氮平的影响。
共纳入72例重度抑郁症患者进行分析。收集潜在的生理生化指标和其他药物联合使用信息，通过建立非线性混合效应（NONMEM）模型来探讨临床奥氮平浓度的影响，并使用蒙特卡罗方法进一步模拟重度抑郁症患者的最佳奥氮平初始剂量。
体重和帕罗西汀的联合使用显著影响奥氮平的清除率。在相同体重下，伴有或不伴有帕罗西汀的重度抑郁症患者奥氮平的清除率之比为0.711:1。对于初始剂量，在不使用帕罗西汀的情况下，对于体重在40至56千克和56至100千克的重度抑郁症患者，建议奥氮平给药剂量分别为0.5和0.4毫克/千克/天。在使用帕罗西汀的情况下，对于体重在40至85千克和85至100千克的重度抑郁症患者，建议奥氮平给药剂量分别为0.3和0.2毫克/千克/天。
这是首次在重度抑郁症患者中建立奥氮平群体药代动力学的案例。此外，本研究创新性地阐明了帕罗西汀对重度抑郁症患者奥氮平群体药代动力学和初始剂量的影响。
