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

Autor: Trogrlić Z; Department of Intensive Care Adults, Erasmus MC University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: z.trogrlic@erasmusmc.nl., van der Jagt M; Department of Intensive Care Adults, Erasmus MC University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: m.vanderjagt@erasmusmc.nl., Osse RJ; Department of Psychiatry, Erasmus MC University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: r.osse@erasmusmc.nl., Devlin JW; School of Pharmacy, Northeastern University, 360 Huntington Ave, Boston, MA 02115, USA. Electronic address: j.devlin@northeastern.edu., Nieboer D; Department of Public Health, Erasmus MC University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: d.nieboer@erasmusmc.nl., Koch BCP; Department of Hospital Pharmacy, Erasmus MC University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: b.koch@erasmusmc.nl., van Schaik RHN; Department of Clinical Chemistry, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: r.vanschaik@erasmusmc.nl., Hunfeld NGM; 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.
Jazyk: angličtina
Zdroj: Journal of critical care [J Crit Care] 2020 Jun; Vol. 57, pp. 203-207. Date of Electronic Publication: 2020 Mar 04.
DOI: 10.1016/j.jcrc.2020.03.001
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: