AUTHOR=Zhang Cun , Jiang Lei , Hu Ke , Zhang Yi-Jia , Han Jing , Chen Jin , Bulubu  , Dong Boling , Shi Hao-Zhe , He Su-Mei , Yu Ting-Ting , Chen Xiao , Wang Dong-Dong 

TITLE=Drug–drug interaction and initial dosage optimization of aripiprazole in patients with schizophrenia based on population pharmacokinetics

JOURNAL=Frontiers in Psychiatry

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1377268

DOI=10.3389/fpsyt.2024.1377268

ISSN=1664-0640

ABSTRACT=Background: The present study was to investigate the drug-drug interaction and initial dosage optimization of aripiprazole in schizophrenia patients based on population pharmacokinetics. 
Research Design and Methods: A total of 119 schizophrenia patients treated by aripiprazole were collected to build aripiprazole population pharmacokinetic model using nonlinear mixed effect. 
Results: Weight and concomitant medication of fluoxetine influenced aripiprazole clearance. Under the same weight, the aripiprazole clearance rates were 0.714:1 in patients with or without fluoxetine, respectively. In addition, without fluoxetine, for once-daily aripiprazole regimen, the dosages of 0.3, and 0.2 mg/kg/day were recommended for patients with schizophrenia with weights of 40-95, and 95-120 kg, respectively; for twice-daily aripiprazole regimen, the dosage of 0.3 mg/kg/day was recommended for patients with schizophrenia with weights of 40-120 kg. With fluoxetine, for once-daily aripiprazole regimen, the dosage of 0.2 mg/kg/day was recommended for patients with schizophrenia with weights of 40-120 kg; for twice-daily aripiprazole regimen, the dosages of 0.3, and 0.2 mg/kg/day were recommended for patients with schizophrenia with weights of 40-60, and 60-120 kg, respectively. 
Conclusion: It was the first time to investigate the effects of fluoxetine on aripiprazole via drug-drug interaction and recommend the optimal aripiprazole initial dosage in patients with schizophrenia.