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J Crit Care. 2020 Mar 4;57:203-207. doi: 10.1016/j.jcrc.2020.03.001. [Epub ahead of print]

Pharmacogenomic response of low dose haloperidol in critically ill adults with delirium.

Author information

1
Department of Intensive Care Adults, Erasmus MC University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: z.trogrlic@erasmusmc.nl.
2
Department of Intensive Care Adults, Erasmus MC University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: m.vanderjagt@erasmusmc.nl.
3
Department of Psychiatry, Erasmus MC University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: r.osse@erasmusmc.nl.
4
School of Pharmacy, Northeastern University, 360 Huntington Ave, Boston, MA 02115, USA. Electronic address: j.devlin@northeastern.edu.
5
Department of Public Health, Erasmus MC University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: d.nieboer@erasmusmc.nl.
6
Department of Hospital Pharmacy, Erasmus MC University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: b.koch@erasmusmc.nl.
7
Department of Clinical Chemistry, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: r.vanschaik@erasmusmc.nl.
8
Department of Intensive Care Adults, Erasmus MC University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands; Department of Hospital Pharmacy, Erasmus MC University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: n.hunfeld@erasmusmc.nl.

Abstract

PURPOSE:

To characterize the pharmacogenomic response of low-dose haloperidol for delirium treatment in critically ill adults.

MATERIALS AND METHODS:

Single-center, pilot study of a convenience sample of ICU adults with delirium treated with low-dose IV haloperidol. Patients were evaluated for delirium with the ICDSC every 8 h. Serum haloperidol concentrations were collected on ICU days 2-6, CYP2D6 and CYP3A4 genotypes were characterized and patients were categorized as extensive (EM), intermediate (IM) or poor metabolizers (PM).

RESULTS:

The 22 patients (median age 67 [IQR 48,77] years; median APACHE III 81[IQR 54,181]; CYP2D6 [EM = 12, IM = 7, PM = 3], CYP3A [EM = 18, IM = 4]) received a median [IQR] daily haloperidol dose of 3.0 [2.4, 4.5] mg. After adjusting for age, SOFA, and ICU day, neither an association between CYP2D6 (IM p = .67/PM p = .25) or CYP3A4 (IM p = .44) metabolizer status and serum haloperidol concentrations was found. After adjusting for age, SOFA, and ICU day, neither an association between daily haloperidol dose (p = .77) or ICDSC score (p = .13) and serum haloperidol concentrations was found. No patient experienced QTc interval prolongation (≥500 ms).

CONCLUSIONS:

This pilot study, the first to evaluate the pharmacogenomic response of low-dose haloperidol when used to treat delirium in the ICU, suggests CYP2D6/CYP3A4 metabolizer status does not affect the serum haloperidol concentrations.

KEYWORDS:

Delirium; Haloperidol; Intensive care; Pharmacodynamics; Pharmacogenetics; Pharmacokinetics

PMID:
32208328
DOI:
10.1016/j.jcrc.2020.03.001

Conflict of interest statement

Declaration of Competing Interest The authors have no competing interests to declare.

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