Abstract | BACKGROUND: METHODS: A physiologically based pharmacokinetic model for OLZ/SAM was developed and validated by comparing model-simulated data with observed clinical data. The model was applied to predict changes in olanzapine and samidorphan pharmacokinetics after administration of OLZ/SAM in subjects with mild, moderate, and severe renal impairment relative to age-matched controls with normal renal function. RESULTS: The model predicted 1.5- and 2.2-fold increases in olanzapine and samidorphan area under the plasma concentration-time curve (AUC), respectively, after a single dose of OLZ/SAM in subjects with severe renal impairment vs controls, which was consistent with results from the clinical study. Application of the model prediction indicated increases in steady-state olanzapine AUC of 1.2-, 1.5-, and 1.6-fold, and samidorphan AUC of 1.4-, 1.8-, and 2.2-fold, in subjects with mild, moderate, and severe renal impairment, respectively, relative to healthy controls. CONCLUSIONS: Physiologically based pharmacokinetic modeling extended the findings from a clinical study in severe renal impairment to other untested clinical scenarios; these data could be of interest to clinicians treating patients with renal impairment.
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Authors | Lei Sun, Lisa von Moltke, Karen Rowland Yeo |
Journal | Clinical pharmacokinetics
(Clin Pharmacokinet)
Vol. 60
Issue 5
Pg. 637-647
(05 2021)
ISSN: 1179-1926 [Electronic] Switzerland |
PMID | 33313995
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antipsychotic Agents
- Narcotic Antagonists
- Naltrexone
- 3-carboxamido-4-hydroxynaltrexone
- Olanzapine
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Topics |
- Antipsychotic Agents
- Area Under Curve
- Humans
- Naltrexone
(analogs & derivatives)
- Narcotic Antagonists
- Olanzapine
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