Pharmacokinetics of Haloperidol in Critically Ill Patients: Is There an Association with Inflammation?

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Abstract

Haloperidol is considered the first-line treatment for delirium in critically ill patients. However, clinical evidence of efficacy is lacking and no pharmacokinetic studies have been performed in intensive care unit (ICU) patients. The aim of this study was to establish a pharmacokinetic model to describe the PK in this population to improve insight into dosing. One hundred and thirty-nine samples from 22 patients were collected in a single-center study in adults with ICU delirium who were treated with low-dose intravenous haloperidol (3-6 mg per day). We conducted a population pharmacokinetic analysis using Nonlinear Mixed Effects Modelling (NONMEM). A one-compartment model best described the data. The mean population estimates were 51.7 L/h (IIV 42.1%) for clearance and 1490 L for the volume of distribution. The calculated half-life was around 22 h (12.3-29.73 h) for an average patient. A negative correlation between C-Reactive Protein (CRP) and haloperidol clearance was observed, where clearance decreased significantly with increasing CRP up to a CRP concentration of 100 mg/L. This is the first step towards haloperidol precision dosing in ICU patients and our results indicate a possible role of inflammation.

Original languageEnglish
Article number549
JournalPharmaceutics
Volume14
Issue number3
DOIs
Publication statusPublished - Mar 2022

Bibliographical note

Funding Information:
Acknowledgments: Letao Li acknowledge the China Scholarship Council for the support by State Scholarship Fund No. 201908500113.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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