{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:19:18Z","timestamp":1790032758222,"version":"4.0.1"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,26]],"date-time":"2023-02-26T00:00:00Z","timestamp":1677369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Metoprolol is a medication commonly utilized in select patients to achieve a reduction in heart rate, systolic blood pressure, or other indications. A majority of metoprolol metabolism occurs via CYP2D6. Decreased expression of the CYP2D6 enzyme increases the concentration of metoprolol. Current pharmacogenomics guidelines by the Dutch Pharmacogenomics Working Group recommend slower titrations and dose decreases to minimize adverse effects from poor metabolizers or normal metabolizers taking concomitant medications that are strong inhibitors of CYP2D6 (phenoconverters). This study aimed to evaluate adverse effects such as bradycardia, hypotension, and syncope in patients who are expected to have absent CYP2D6 enzyme activity due to drug\u2013drug or drug\u2013gene interactions. The secondary aims of this study were to evaluate heart rate measurements for the included participants. Retrospective data were collected for individuals with CYP2D6 genotyping results obtained for clinical purposes. Three categories (CYP2D6 normal metabolizers, poor metabolizers, and phenoconverters) were assigned. A total of 325 participants were included. There was no statistically significant difference found in the primary composite outcome between the three metabolizer groups (p = 0.054). However, a statistically significant difference was identified in the incidences of bradycardia between the poor metabolizers and the normal metabolizers or phenoconverters (p &lt; 0.0001). The average heart rates were 2.8 beats per minute (bpm) and 2.6 bpm lower for the poor metabolizer and phenoconverter groups, respectively, compared to the normal metabolizers (p &lt; 0.0001 for both comparisons). This study further supports the role of genetic testing in precision medicine to help individualize patient care as CYP2D6 poor metabolizers taking metoprolol were found to have an increase in bradycardia. Additional research is needed to clarify the dose relationship in this drug\u2013gene interaction.<\/jats:p>","DOI":"10.3390\/jpm13030416","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T02:22:16Z","timestamp":1677464536000},"page":"416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Metoprolol and CYP2D6: A Retrospective Cohort Study Evaluating Genotype-Based Outcomes"],"prefix":"10.3390","volume":"13","author":[{"given":"Savannah","family":"Collett","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Services, Sanford USD Medical Center, Sioux Falls, SD 57117, USA"},{"name":"Roger Maris Cancer Center, Sanford Medical Center, Fargo, ND 58102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5401-5318","authenticated-orcid":false,"given":"Amanda","family":"Massmann","sequence":"additional","affiliation":[{"name":"Sanford Imagenetics, Sanford Health, Sioux Falls, SD 57105, USA"},{"name":"Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha J.","family":"Petry","sequence":"additional","affiliation":[{"name":"Sanford Imagenetics, Sanford Health, Sioux Falls, SD 57105, USA"},{"name":"Department of Pharmacy Practice, North Dakota State University, Fargo, ND 58108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Van Heukelom","sequence":"additional","affiliation":[{"name":"Sanford Imagenetics, Sanford Health, Sioux Falls, SD 57105, USA"},{"name":"Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1249-3685","authenticated-orcid":false,"given":"April","family":"Schultz","sequence":"additional","affiliation":[{"name":"Sanford Imagenetics, Sanford Health, Sioux Falls, SD 57105, USA"},{"name":"Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadd","family":"Hellwig","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Services, Sanford USD Medical Center, Sioux Falls, SD 57117, USA"},{"name":"College of Pharmacy & Allied Health Professions, South Dakota State University, Brookings, SD 57007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4849-5415","authenticated-orcid":false,"given":"Jordan F.","family":"Baye","sequence":"additional","affiliation":[{"name":"Sanford Imagenetics, Sanford Health, Sioux Falls, SD 57105, USA"},{"name":"Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA"},{"name":"College of Pharmacy & Allied Health Professions, South Dakota State University, Brookings, SD 57007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1056\/NEJM198212163072505","article-title":"Oxidation Phenotype\u2014A Major Determinant of Metoprolol Metabolism and Response","volume":"307","author":"Lennard","year":"1982","journal-title":"N. 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