Zhang Cun, Jiang Lei, Hu Ke, Chen Liang, Zhang Yi-Jia, Shi Hao-Zhe, He Su-Mei, Chen Xiao, Wang Dong-Dong
Department of Pharmacy, Xuzhou Oriental Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy & School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.
Neuropsychiatr Dis Treat. 2024 Mar 4;20:479-490. doi: 10.2147/NDT.S455183. eCollection 2024.
Olanzapine has already been used to treat schizophrenia patients; however, the initial dosage recommendation when multiple drugs are used in combination, remains unclear. The purpose of this study was to explore the drug-drug interaction (DDI) of multiple drugs combined with olanzapine and to recommend the optimal administration of olanzapine in schizophrenia patients.
In this study, we obtained olanzapine concentrations from therapeutic drug monitoring (TDM) database. In addition, related medical information, such as physiological, biochemical indexes, and concomitant drugs was acquired using medical log. Sixty-five schizophrenia patients were enrollmented for analysis using population pharmacokinetic model by means of nonlinear mixed effect (NONMEM).
Weight and combined use of aripiprazole significantly affected olanzapine clearance. Without aripiprazole, for once-daily olanzapine administration dosages, 0.6, 0.5 mg/kg/day were recommended for 40-70, and 70-100 kg schizophrenia patients, respectively; for twice-daily olanzapine administration dosages, 0.6, 0.5 mg/kg/day were recommended for 40-60, and 60-100 kg schizophrenia patients, respectively. With aripiprazole, for once-daily olanzapine administration dosages, 0.4, 0.3 mg/kg/day were recommended for 40-53, and 53-100 kg schizophrenia patients, respectively; for twice-daily olanzapine administration dosages, 0.4 mg/kg/day was recommended for 40-100 kg schizophrenia patients, respectively.
Aripiprazole significantly affected olanzapine clearance, and when schizophrenia patients use aripiprazole, the olanzapine dosages need adjust. Meanwhile, we firstly recommended the optimal initial dosages of olanzapine in schizophrenia patients.
奥氮平已用于治疗精神分裂症患者；然而，多种药物联合使用时的初始剂量推荐仍不明确。本研究的目的是探讨多种药物与奥氮平联合使用时的药物相互作用（DDI），并为精神分裂症患者推荐奥氮平的最佳给药方案。
在本研究中，我们从治疗药物监测（TDM）数据库中获取奥氮平浓度。此外，使用医疗日志获取相关医学信息，如生理、生化指标和合并用药情况。纳入65例精神分裂症患者，采用非线性混合效应（NONMEM）的群体药代动力学模型进行分析。
体重和阿立哌唑的联合使用显著影响奥氮平清除率。不使用阿立哌唑时，对于每日一次服用奥氮平的剂量，40 - 70 kg和70 - 100 kg的精神分裂症患者分别推荐0.6、0.5 mg/kg/天；对于每日两次服用奥氮平的剂量，40 - 60 kg和60 - 100 kg的精神分裂症患者分别推荐0.6、0.5 mg/kg/天。使用阿立哌唑时，对于每日一次服用奥氮平的剂量，40 - 53 kg和53 - 100 kg的精神分裂症患者分别推荐0.4、0.3 mg/kg/天；对于每日两次服用奥氮平的剂量，40 - 100 kg的精神分裂症患者均推荐0.4 mg/kg/天。
阿立哌唑显著影响奥氮平清除率，精神分裂症患者使用阿立哌唑时，奥氮平剂量需要调整。同时，我们首次推荐了精神分裂症患者奥氮平的最佳初始剂量。
