{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T22:00:52Z","timestamp":1765231252008,"version":"3.37.3"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Shriner\u2019s Developmental grant"},{"name":"Shriner\u2019s Clinical Research grant"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["1K01OD026608-01"],"award-info":[{"award-number":["1K01OD026608-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Career Development"},{"name":"NIH Clinical Research Loan Repayment Program Award"},{"name":"UC Davis Comprehensive Cancer Center Support"},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["NCI P30CA093373"],"award-info":[{"award-number":["NCI P30CA093373"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Management of critically ill patients requires simultaneous administration of many medications. Treatment for patient comorbidities may lead to drug\u2013drug interactions which decrease drug efficacy or increase adverse reactions. Current practices rely on a one-size-fits-all dosing approach. Pharmacogenetic testing is generally reserved for addressing problems rather than used proactively to optimize care. We hypothesized that burn and surgery patients will have one or more genetic variants in drug metabolizing pathways used by one or more medications administered during the patient\u2019s hospitalization. The aim of this study was to determine the frequency of variants with abnormal function in the primary drug pathways and identify which medications may be impacted. Genetic (19 whole exome and 11 whole genome) and medication data from 30 pediatric burn and surgery patients were analyzed to identify pharmacogene\u2013drug associations. Nineteen patients were identified with predicted altered function in one or more of the following genes: CYP2C9, CYP2C19, CYP2D6, and CYP3A4. The majority had decreased function, except for several patients with CYP2C19 rapid or ultrarapid variants. Some drugs administered during hospitalization that rely on these pathways include hydrocodone, oxycodone, methadone, ibuprofen, ketorolac, celecoxib, diazepam, famotidine, diphenhydramine, and glycopyrrolate. Approximately one-third of the patients tested had functionally impactful genotypes in each of the primary drug metabolizing pathways. This study suggests that genetic variants may in part explain the vast variability in drug efficacy and suggests that future pharmacogenetics research may optimize dosing regimens.<\/jats:p>","DOI":"10.1093\/jbcr\/irac062","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T11:40:20Z","timestamp":1652182820000},"page":"987-996","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacogenetic Gene\u2013Drug Associations in Pediatric Burn and Surgery Patients"],"prefix":"10.1093","volume":"43","author":[{"given":"Kristin N","family":"Grimsrud","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan R","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clifford G","family":"Tepper","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina L","family":"Palmieri","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, University of California, Davis , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"key":"2022090113593217600_CIT0001","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.pharmthera.2012.12.007","article-title":"Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation","volume":"138","author":"Zanger","year":"2013","journal-title":"Pharmacol Ther"},{"key":"2022090113593217600_CIT0002","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/03602530902843483","article-title":"Polymorphism of human cytochrome P450 enzymes and its clinical impact","volume":"41","author":"Zhou","year":"2009","journal-title":"Drug Metab Rev"},{"key":"2022090113593217600_CIT0003","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.clinbiochem.2014.05.065","article-title":"Pharmacogenetics of chronic pain management","volume":"47","author":"Kapur","year":"2014","journal-title":"Clin Biochem"},{"key":"2022090113593217600_CIT0004","first-page":"932","article-title":"Metabolism of fentanyl, a synthetic opioid analgesic, by human liver microsomes. 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