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. 2019 Jan 24;59(5):731–747. doi: 10.1002/jcph.1365

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© 2019, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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Predicting the impact of dose adjustment on plasma PK and receptor occupancy (RO) according to the clinical trial of Nyberg et al. Eight schizophrenic patients first received risperidone oral dose at 6 mg/day (2 times daily) for 28 days, which was then reduced to 3 mg/day (2 times daily) for 14 days. (A) Observed (dots) and predicted (arithmetic mean as gray lines) plasma concentration‐time profiles of the total active moiety (risperidone plus paliperidone). (B) Observed (dots, mean ± range) and predicted (arithmetic mean as black line with 95% confidence interval) D2 RO. (C) Predicted RO‐time profiles on D2 (black line) and non‐D2 receptors (serotonin 5‐HT_2A, green; adrenergic alpha‐1A, blue; alpha‐2, yellow; histamine H1, gray) in the brain. The observed RO of 5‐HT_2A (green dots, mean ± range) was also shown.