• Zoran Trogrlić, Mathieu van der Jagt, Robert Jan Osse, John W Devlin, Daan Nieboer, Koch Birgit C P BCP Department of Hospital Pharmacy, Erasmus MC University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic addres, van Schaik Ron H N RHN Department of Clinical Chemistry, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic addre, and Hunfeld Nicole G M NGM Department of Intensive Care Adults, Erasmus MC University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands; Department.
• Department of Intensive Care Adults, Erasmus MC University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: z.trogrlic@erasmusmc.nl.
• J Crit Care. 2020 Jun 1; 57: 203-207.

PurposeTo characterize the pharmacogenomic response of low-dose haloperidol for delirium treatment in critically ill adults.Materials And MethodsSingle-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).ResultsThe 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).ConclusionsThis 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.Copyright © 2020 Elsevier Inc. All rights reserved.

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