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.

Background The substantial health damage attributed to heat waves, along with their increasing intensity and frequency in the context of global warming, highlights the importance of exploring the health effects of heat waves. Objective To calculate the excess heat stroke cases during heat waves in the summer of 2013—2023 in Shanghai, analyze the association between heat waves and heat stroke, and to further explore the modifying effects of heat wave characteristics on heat stroke. Methods Using a retrospective ecological study design, data on heat stroke cases were collected from the heat stroke case reporting system of the Chinese Center for Disease Control and Prevention, and concurrent meteorological data from Xujiahui Meteorological Station. A heat wave was defined as at least 3 consecutive days with daily maximum temperature meeting or exceeding 35 ℃ in this study, excess heat stroke cases related to heat waves were assessed as the difference between the numbers of heat stroke cases observed on a given day and the corresponding 31 d (15 d before and after that day) moving average, and statistical analyses using generalized linear model based on time series study were performed to assess the impact of heat waves on heat stroke. Results Overall 25 heat waves during the study period were observed, leading to a total of estimated 792.6 extra heat stroke cases. The risk of heat stroke significantly increased during heat waves (RR=2.60, 95%CI: 2.08, 3.26), but no statistically significant differences in heat wave effects were observed among different genders, ages, or regions. In terms of the timing of heat waves, the risk of heat stroke was highest during the first heat wave (RR=3.58, 95%CI: 2.82, 4.55), which was significantly higher than that during the second heat wave (RR=2.19, 95%CI: 1.66, 2.90), and no significant effect was observed during the third or subsequent heat waves. The impact of heat waves on heat stroke persisted for more than 4 d, with the risk higher on the fourth day and beyond (RR=2.95, 95%CI: 2.28, 3.83), significantly higher than on the first day of heat wave (RR=1.74, 95%CI: 1.18, 2.56). Conclusion Heat waves had a substantial effect on heat stroke in Shanghai from 2013 to 2023, and special attention need to be paid to heat waves with early onset and long duration.