Xiao Chen,1,* Yue Zhang,2,* Di Yin,3,* Ying-Wei Jin,2,4,* Su-Mei He,5 Cun Zhang,6 Dong-Dong Wang2 

1School of Nursing, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 2School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 3Department of Pharmacy, Wuxi Maternity and Child Health Care Hospital, Wuxi, Jiangsu, 214002, People’s Republic of China; 4Department of Pharmacy, The Suqian Clinical College of Xuzhou Medical University, Suqian, Jiangsu, 223800, People’s Republic of China; 5Department of Pharmacy, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, Jiangsu, 215153, People’s Republic of China; 6Department of Pharmacy, Xuzhou Oriental Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Su-Mei He, Email hehe8204@163.com

Objective: Quetiapine has been used for treating patients with depression; however, drug-drug interactions (DDIs) deeply limit its individualized administration. This study explored DDIs and initial dose recommendation of quetiapine in depression patients based on real-world data.
Methods: Sixty-four real-world depression patients were used to investigate the effects of drug combinations on quetiapine using a non-linear mixed effect model (NONMEM).
Results: In the final model, paroxetine and fluvoxamine were included as covariates, which significantly affected the clearance rate of quetiapine, with ratios of about 1.00:0.54:0.48:0.26 in patients with depression who were not accompanied by paroxetine or fluvoxamine, patients with depression who were accompanied by paroxetine, patients with depression who were accompanied by fluvoxamine, and patients with depression who were accompanied by paroxetine and fluvoxamine. Furthermore, the initial dose optimizations of quetiapine were 20 and 16 mg/kg/day for depression patients not accompanied by paroxetine or fluvoxamine who weighted 40– 80, and 80– 120 kg, respectively. The initial dose of quetiapine was 8 mg/kg/day for depression patients accompanied by paroxetine who weighted 40– 120 kg. The initial dose of quetiapine was 8 mg/kg/day for depression patients accompanied by fluvoxamine, who weighted 40– 120 kg. The initial dose optimization of quetiapine was 4 mg/kg/day for depression patients accompanied by paroxetine and fluvoxamine who weighted 40– 120 kg.
Conclusion: Our study explored DDIs and initial dose recommendation of quetiapine in depression patients from the real world, and the initial dose optimization of quetiapine was recommended based on the interaction with paroxetine or fluvoxamine.

Keywords: drug-drug interactions, initial dose recommendation, quetiapine, depression patients, real world