Analysis of Oral Absorption and Dietary Effects of Rosuvastatin Based on Physiologically Based Pharmacokinetic Model
10.13748/j.cnki.issn1007-7693.20230574
- VernacularTitle:基于生理药动学模型的瑞舒伐他汀口服吸收及饮食影响分析
- Author:
Yewen SUN
1
;
Yuchen QU
2
;
Jie PAN
2
;
Yunli YU
2
Author Information
1. School of Pharmacy, Soochow University, Suzhou 215127, China
2. Department of Pharmacy, The Second Affiliated Hospital of Suzhou University, Suzhou 215004, China
- Publication Type:Journal Article
- Keywords:
physiologically based pharmacokinetic model ；rosuvastatin； food effect
- From:
Chinese Journal of Modern Applied Pharmacy
2024;41(8):1021-1026
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE :To construct physiologically based pharmacokinetic model(PBPK) model of rosuvastatin in fasting state to predict its absorption in postprandial state and explore its possible food effect mechanism. At the same time, reasonable dietary suggestions were put forward for hyperlipidemia patients taking statins to improve the absorption of BCS Ⅲ statins.
METHODS
According to the literature and existing research, the physicochemical parameters, biopharmaceutical parameters and pharmacokinetic parameters of rosuvastatin modeling were obtained. The PBPK prediction model of rosuvastatin postprandial administration was established by GastroPlusTM software, and the model was verified by the measured blood concentration data to determine whether the drug absorption results of rosuvastatin postprandial can be accurately predicted, and the parameter sensitivity analysis was carried out.
RESULTS
The PBPK model of rosuvastatin was constructed to predict its postprandial absorption. The average folding error and absolute average folding error of the model prediction data and the measured data were calculated to be less than 2, and the fitting correlation coefficient combined with model verification showed that the fitting was good. At the same time, parameter sensitivity analysis showed that high-calorie diet, drug LogD and permeability had a greater impact on the absorption of rosuvastatin.
CONCLUSION
The established model can better predict the absorption of rosuvastatin after meals. Based on the results of parameter sensitivity analysis, reasonable dietary recommendations are proposed for hyperlipidemia patients taking BCSⅢ statins, including appropriately increasing the proportion of protein in the diet, reducing the proportion of fat and water-soluble dietary fiber, etc., to improve the intestinal absorption of BCSⅢ statins.
