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. 2015 Jul 24;4(8):454–464. doi: 10.1002/psp4.12007

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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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Twenty-four hour fluctuation for oral bioavailability (F) and clearance (CL) according to the final model with the 95% confidence interval of the empirical Bayes estimates (EBEs) for F (IIV+IOV) and CL (IIV) at each administration time. For oral bioavailability, the time of the peak was estimated at 12:14 with an estimated amplitude of 0.041 (14.7% increase) (upper panel). For clearance, the time of the peak was estimated at 18:50 with an estimated amplitude of 0.027 L/min (7.2% increase) (lower panel).