Drug-Drug Interactions and Initial Dosage Optimization of Quetiapine in Patients with Depression: A Real-World Study.

IF 5.1 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-09-09 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S538856

Xiao Chen, Yue Zhang, Di Yin, Ying-Wei Jin, Su-Mei He, Cun Zhang, Dong-Dong Wang

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引用次数: 0

Abstract

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.

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喹硫平在抑郁症患者中的药物相互作用和初始剂量优化：一项现实世界研究。

目的：喹硫平治疗抑郁症；然而，药物相互作用（ddi）严重限制了其个体化给药。本研究基于真实数据探讨了喹硫平在抑郁症患者中的ddi和初始推荐剂量。方法：采用非线性混合效应模型（NONMEM）研究64例现实世界抑郁症患者联合用药对喹硫平的影响。结果：最终模型纳入帕罗西汀和氟伏沙明作为协变量，显著影响喹硫平清除率，在不伴帕罗西汀和氟伏沙明的抑郁症患者、伴帕罗西汀的抑郁症患者、伴氟伏沙明的抑郁症患者、伴帕罗西汀和伴氟伏沙明的抑郁症患者中，二者的比值约为1.00:0.54:0.48:0.26。此外，对于体重分别为40-80 kg和80-120 kg的不伴有帕罗西汀或氟伏沙明的抑郁症患者，喹硫平的初始最佳剂量分别为20和16 mg/kg/天。体重40-120 kg伴有帕罗西汀的抑郁症患者，喹硫平初始剂量为8mg /kg/天。伴有氟伏沙明的抑郁症患者初始剂量为8 mg/kg/天，体重40-120 kg。体重40 ~ 120 kg伴有帕罗西汀和氟伏沙明的抑郁症患者，喹硫平的初始最佳剂量为4 mg/kg/d。结论：我们的研究从现实世界中探索了喹硫平在抑郁症患者中的ddi和初始剂量推荐，并根据喹硫平与帕罗西汀或氟伏沙明的相互作用推荐喹硫平的初始剂量优化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.