{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:11:43Z","timestamp":1790687503074,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,9,6]],"date-time":"2017-09-06T00:00:00Z","timestamp":1504656000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["U01HG008701\u201002S1"],"award-info":[{"award-number":["U01HG008701\u201002S1"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["U01HG007278"],"award-info":[{"award-number":["U01HG007278"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>\n                    Opioid analgesics are the standards of care for the treatment of moderate to severe nociceptive pain, particularly in the setting of cancer and surgery. Their analgesic properties mainly emanate from stimulation of the \u03bc receptors, which are encoded by the\n                    <jats:italic>OPRM1<\/jats:italic>\n                    gene. Hepatic metabolism represents the major route of elimination, which, for some opioids, namely codeine and tramadol, is necessary for their bioactivation into more potent analgesics. The highly polymorphic nature of the genes coding for phase I and phase II enzymes (pharmacokinetics genes) that are involved in the metabolism and bioactivation of opioids suggests a potential interindividual variation in their disposition and, most likely, response. In fact, such an association has been substantiated in several pharmacokinetic studies described in this review, in which drug exposure and\/or metabolism differed significantly based on the presence of polymorphisms in these pharmacokinetics genes. Furthermore, in some studies, the observed variability in drug exposure translated into differences in the incidence of opioid\u2010related adverse effects, particularly nausea, vomiting, constipation, and respiratory depression. Although the influence of polymorphisms in pharmacokinetics genes, as well as pharmacodynamics genes (\n                    <jats:italic>OPRM1<\/jats:italic>\n                    and\n                    <jats:italic>COMT<\/jats:italic>\n                    ) on response to opioids has been a subject of intense research, the results have been somehow conflicting, with some evidence insinuating for a potential role for\n                    <jats:italic>OPRM1<\/jats:italic>\n                    . The Clinical Pharmacogenetics Implementation Consortium guidelines provide\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    \u2010guided therapeutic recommendations to individualize treatment with tramadol and codeine. However, implementation guidelines for other opioids, which are more commonly used in real\u2010world settings for pain management, are currently lacking. Hence, further studies are warranted to bridge this gap in our knowledge base and ultimately ascertain the role of pharmacogenetic markers as predictors of response to opioid analgesics.\n                  <\/jats:p>","DOI":"10.1002\/phar.1986","type":"journal-article","created":{"date-parts":[[2017,7,12]],"date-time":"2017-07-12T08:12:39Z","timestamp":1499847159000},"page":"1105-1121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":149,"title":["Review of Opioid Pharmacogenetics and Considerations for Pain Management"],"prefix":"10.1002","volume":"37","author":[{"given":"Aniwaa","family":"Owusu Obeng","sequence":"first","affiliation":[{"name":"The Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai New York NY"},{"name":"Pharmacy Department The Mount Sinai Hospital New York New York"},{"name":"Division of General Internal Medicine Department of Medicine Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issam","family":"Hamadeh","sequence":"additional","affiliation":[{"name":"Levine Cancer Institute Charlotte North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Smith","sequence":"additional","affiliation":[{"name":"University of Michigan College of Pharmacy Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,6]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15817"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/104990910402100213"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000068822.10113.9E"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.157"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.DMPK-11-RG-134"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69255-6"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2006.03.018"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.36076\/ppj.2008\/11\/S133"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)03167-6"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.2217\/14622416.6.8.849"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.2165\/11318030-000000000-00000"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0b013e318160f827"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(98)00021-9"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2007.01.049"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e3182272b10"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2015.3"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31824a1e21"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2006.02182.x"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.287"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.254"},{"key":"e_1_2_12_22_1","unstructured":"U.S. Food and Drug Administration.FDA Drug Safety Communication: FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women.2017."},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e318273f2c7"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.09.004"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.2217\/14622416.9.11.1605"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aep192"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2013.11.015"},{"issue":"3","key":"e_1_2_12_28_1","first-page":"E227","article-title":"The role of hydromorphone and OPRM1 in postoperative pain relief with hydrocodone","volume":"16","author":"Boswell MV","year":"2013","journal-title":"Pain Physician"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-1907"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2013.00024"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.064352"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2006.09.012"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000000867"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.tpj.6500406"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100385"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2006.01.007"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2014.56"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2006.10.023"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2005.03.032"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.14.100"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2013.14.5.2937"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-6576.2004.00517.x"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-6576.2006.01058.x"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200210000-00011"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200608000-00016"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318182af21"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-002-0490-1"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21051"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010397729"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010388033"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-011-1093-5"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-6576.2009.02104.x"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00673.x"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060239"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1993.43"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2014.09.002"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100152"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-006-0135-x"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03256239"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0b013e31817b796e"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.26430"},{"issue":"2","key":"e_1_2_12_62_1","first-page":"106","article-title":"(TA)8 allele in the UGT1A1 gene promoter of a Caucasian with Gilbert's syndrome","volume":"84","author":"Iolascon A","year":"1999","journal-title":"Haematologica"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.14.8170"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2011.01.040"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-4-64"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/518012"},{"key":"e_1_2_12_67_1","unstructured":"U.S. Food and Drug Administration. FDA Drug Safety Communication: Safety review update of codeine use in children; new Boxed Warning and Contraindication on use after tonsillectomy and\/or adenoidectomy. Rockville MD [updated 1\/15\/2016]. Available from:http:\/\/www.fda.gov\/Drugs\/DrugSafety\/ucm339112.htm. Accessed November 1 2016."}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fphar.1986","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.1986","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T10:05:35Z","timestamp":1761041135000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.1986"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9]]},"references-count":66,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1002\/phar.1986"],"URL":"https:\/\/doi.org\/10.1002\/phar.1986","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9]]},"assertion":[{"value":"2017-09-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}