| Autor: |
MOU Fan, HUANG Zhiwei, CHENG Yu, ZHAO Xue, LI Huafang, YU Shunying |
| Jazyk: |
čínština |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Shanghai Jiaotong Daxue xuebao. Yixue ban, Vol 44, Iss 11, Pp 1414-1421 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1674-8115 |
| DOI: |
10.3969/j.issn.1674-8115.2024.11.008 |
| Popis: |
Objective·To develop physiologically based pharmacokinetic (PBPK) models specifically designed for the Chinese population by utilizing the combination of clozapine and fluvoxamine as a case, and predict the drug-drug interaction (DDI) associated with the combination medication of clozapine, ultimately optimizing the dosage of clozapine.Methods·By obtaining the physicochemical parameters, absorption, distribution, metabolism, excretion (ADME)-related parameters, and physiologically relevant parameters of the Chinese population through literature and pharmacology-related databases, PBPK models for the clozapine and fluvoxamine were constructed by using PK-Sim® software. The models′ accuracy was evaluated by comparing predicted values of the area under the curve (AUC) and peak concentration (Cmax) to observed data, using the mean percentage error (MPE) and mean absolute percentage error (MAPE) as evaluation indicators. The models were validated against real-world plasma drug concentration data. Additionally, combining the inhibitory effect of fluvoxamine on clozapine, models for the combination therapy of clozapine and fluvoxamine were developed to predict the pharmacokinetic changes of clozapine. The presence of clinically significant DDI was determined by using the 90% confidence interval of the AUC ratio (AUCR) or Cmax ratio (CmaxR) as evaluation metrics, with a non-effect boundary set at 80%‒125%. The pharmacokinetic changes of clozapine upon co-administration with fluvoxamine based on PBPK models were quantified, and a dosage optimization for clozapine was developed.Results·The constructed model of clozapine and fluvoxamine was considered accurate if the absolute value of the MPE was ≤10% and the MAPE was |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
