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• W2802832835 abstract "It was recently reported that the Cmax and AUC of rosuvastatin increases when it is coadministered with telmisartan and cyclosporine. Rosuvastatin is known to be a substrate of OATP1B1, OATP1B3, NTCP, and BCRP transporters. The aim of this study was to explore the mechanism of the interactions between rosuvastatin and two perpetrators, telmisartan and cyclosporine. Published (cyclosporine) or newly developed (telmisartan) PBPK models were used to this end. The rosuvastatin model in Simcyp (version 15)'s drug library was modified to reflect racial differences in rosuvastatin exposure. In the telmisartan–rosuvastatin case, simulated rosuvastatin CmaxI/Cmax and AUCI/AUC (with/without telmisartan) ratios were 1.92 and 1.14, respectively, and the Tmax changed from 3.35 h to 1.40 h with coadministration of telmisartan, which were consistent with the aforementioned report (CmaxI/Cmax: 2.01, AUCI/AUC:1.18, Tmax: 5 h → 0.75 h). In the next case of cyclosporine–rosuvastatin, the simulated rosuvastatin CmaxI/Cmax and AUCI/AUC (with/without cyclosporine) ratios were 3.29 and 1.30, respectively. The decrease in the CLint,BCRP,intestine of rosuvastatin by telmisartan and cyclosporine in the PBPK model was pivotal to reproducing this finding in Simcyp. Our PBPK model demonstrated that the major causes of increase in rosuvastatin exposure are mediated by intestinal BCRP (rosuvastatin–telmisartan interaction) or by both of BCRP and OATP1B1/3 (rosuvastatin–cyclosporine interaction)." @default.
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• W2802832835 date "2018-01-01" @default.
• W2802832835 modified "2023-10-16" @default.
• W2802832835 title "Physiologically-based pharmacokinetic predictions of intestinal BCRP-mediated drug interactions of rosuvastatin in Koreans" @default.
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• W2802832835 doi "https://doi.org/10.4196/kjpp.2018.22.3.321" @default.
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