2026-05-31T09:36:45Z https://repub.eur.nl/oai

oai:repub.eur.nl:125718 2023-11-26T18:42:17Z

urn:NBN:nl:ui:15-1765/125718 2023-11-26T18:42:17 mods http://hdl.handle.net/1765/125718 hdl:1765/125718 urn:NBN:nl:ui:15-1765/125718 doi:10.1016/j.jcrc.2020.03.001 http://hdl.handle.net/1765/125718 https://repub.eur.nl/pub/125718/Repub_125718.pdf application/pdf Filesize: 860085 bytes born digital Department of Intensive Care sht supporting host Department of Psychiatry sht supporting host Department of Public Health sht supporting host Department of Pharmacy sht supporting host Department of Clinical Chemistry sht supporting host Z. Trogrlić (Zoran) Trogrlić Zoran aut author M. van der Jagt (Mathieu) Jagt Mathieu aut author R.J. Osse (Robert Jan) Osse Robert Jan aut author Devlin, J.W. (John W.) Devlin J.W. (John W.) aut author D. Nieboer (Daan) Nieboer Daan aut author B.C.P. Koch (Birgit) Koch Birgit aut author R.H.N. van Schaik (Ron) Schaik Ron aut author N.G.M. Hunfeld (Nicole) Hunfeld Nicole aut author 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. Journal of Critical Care: improving patient care by integrating critical care systems knowledge into practice behavior 10739 08839441 57 203 207 2020-06-01 en English Delirium Haloperidol Intensive care Pharmacodynamics Pharmacogenetics Pharmacokinetics Pharmacogenomic response of low dose haloperidol in critically ill adults with delirium text info:eu-repo/semantics/article 294231277 213060752 101870752 http://purl.org/eprint/accessRights/OpenAccess