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. 2015 Nov 28;4(12):701–710. doi: 10.1002/psp4.12047

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© 2015 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

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Geometric mean concentration–time profile of (a) raloxifene, (b) raloxifene‐4′‐glucuronide (R4G), and (c) raloxifene‐6‐glucuronide (R6G) following a single 60 mg oral dose of raloxifene given alone (open symbols) or after silibinin (480 mg three times daily × 4 days) treatment (solid symbols). Lines in (a) denote PBPK model simulations of raloxifene concentration–time profiles when given alone (solid line) or with silibinin (dashed line) using Berkeley Madonna (gray) or SimCYP (crimson). R6G concentrations are not reported beyond 72 hours due to concentrations being below the lower limit of quantitation (c). Symbols and error bars denote observed geometric means and upper limits of the 90% confidence interval, respectively.