Pharmacogenomic response of low dose haloperidol in critically ill adults with delirium
Autor: | Mathieu van der Jagt, John W. Devlin, Zoran Trogrlić, Birgit C. P. Koch, Nicole G. M. Hunfeld, Ron H.N. van Schaik, Robert Jan Osse, Daan Nieboer |
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Přispěvatelé: | Intensive Care, Psychiatry, Public Health, Pharmacy, Clinical Chemistry |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Adult
Male CYP2D6 Genotype Critical Illness Pilot Projects Critical Care and Intensive Care Medicine behavioral disciplines and activities Pharmacokinetics Intensive care medicine Haloperidol Cytochrome P-450 CYP3A Humans Prospective Studies Aged business.industry Delirium Middle Aged Cytochrome P-450 CYP2D6 Pharmacogenetics Anesthesia Pharmacodynamics Pharmacogenomics Female medicine.symptom business Antipsychotic Agents medicine.drug |
Zdroj: | Journal of Critical Care, 57, 203-207. Elsevier |
ISSN: | 0883-9441 |
Popis: | 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. |
Databáze: | OpenAIRE |
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