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The compounds [solubility\u2010limited concentration (\u03bcM) studied] were as follows: baclofen (1000), carisoprodol (200), its metabolite meprobamate (1000), chlorzoxazone (200), cyclobenzaprine (1000), metaxalone (50), methocarbamol (1000), orphenadrine (1000) and tizanidine (1000). Compounds were first incubated with human liver microsomes \u00b1 pre\u2010incubation, screened with pathway\u2010specific c<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010expressed cytochrome P450s (r<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>), and then <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content><jats:sub>50<\/jats:sub> values determined using either 8\u2010concentration tests for those where the r<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content> screen suggested an <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content><jats:sub>50<\/jats:sub> was achievable, or a 3\u2010concentration test with downward extrapolation if screen suggested 50% inhibition was not achievable. These results were then extrapolated to determine an inhibitory potential. Six pathway inhibitor combinations were identified with a moderate inhibitory potential (\u22652.0 &lt; 5.0): five with chlorzoxazone, R\u2010<jats:styled-content style=\"fixed-case\">EDDP<\/jats:styled-content>, S\u2010<jats:styled-content style=\"fixed-case\">EDDP<\/jats:styled-content> and noroxycodone production by <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4, and R\u2010 and S\u2010<jats:styled-content style=\"fixed-case\">EDDP<\/jats:styled-content> production by <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>2B6; and one for the meprobamate effect on noroxycodone production by <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4. An additional eleven combinations were found with a weak inhibitory potential (\u22651.25 &lt; 2.0): five with carisoprodol, two each with methocarbamol and meprobamate, and one each with metaxalone and orphenadrine. This represents the first comprehensive study of the inhibitory effect of this class of drugs and suggests that some of them may produce significant drug\u2013drug interactions with opioids that are frequent comedications with skeletal muscle relaxants.<\/jats:p>","DOI":"10.1111\/bcpt.12999","type":"journal-article","created":{"date-parts":[[2018,3,5]],"date-time":"2018-03-05T11:16:48Z","timestamp":1520248608000},"page":"327-334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inhibition of <i>In Vitro<\/i> Metabolism of Opioids by Skeletal Muscle Relaxants"],"prefix":"10.1111","volume":"123","author":[{"given":"David E.","family":"Moody","sequence":"first","affiliation":[{"name":"Center for Human Toxicology Department of Pharmacology and Toxicology University of Utah Salt Lake City UT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueqiao","family":"Fu","sequence":"additional","affiliation":[{"name":"Center for Human Toxicology Department of Pharmacology and Toxicology University of Utah Salt Lake City UT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenfang B.","family":"Fang","sequence":"additional","affiliation":[{"name":"Center for Human Toxicology Department of Pharmacology and Toxicology University of Utah Salt Lake City UT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,19]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"849","article-title":"Increases in heroin overdose deaths \u2013 28 States, 2010 to 2012","volume":"63","author":"Rudd RA","year":"2014","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/15360288.2015.1037521"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(11)60750-7"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2012.08.013"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/bkt060"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/bkv030"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ftd.0000197094.92559.b4"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/32.3.208"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/bkt042"},{"key":"e_1_2_7_11_1","first-page":"427","article-title":"Considerations for the appropriate use of skeletal muscle relaxants for the management of acute low back pain","volume":"39","author":"Witenko C","year":"2014","journal-title":"Pharm Ther"},{"key":"e_1_2_7_12_1","unstructured":"FrydrychV OdertaG.Skeletal muscle relaxants drug class review (a report prepared for the Utah Department of Health).https:\/\/medicaid.utah.gov\/pharmacy\/ptcommittee\/files\/CriteriaReview Documents\/2016\/.02 Skeletal Muscle Relaxant Class Review.pdf.2016"},{"key":"e_1_2_7_13_1","first-page":"390","article-title":"Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes","volume":"25","author":"Guo Z","year":"1997","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2002.5673"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1851"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(73)90196-2"},{"key":"e_1_2_7_17_1","volume-title":"Guidance for Industry, Drug Interaction Studies \u2013 Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations","author":"FDA US","year":"2012"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00637624"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270002042001007"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00613463"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajps.2016.01.002"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-199610000-00002"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600720905"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1993.85"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00280060"},{"issue":"11","key":"e_1_2_7_26_1","first-page":"S29","article-title":"Pharmacokinetics and pharmacodynamics of tizanidine","volume":"44","author":"Roberts RC","year":"1994","journal-title":"Neurology"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.105.003681"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.117580"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2006.01.009"}],"container-title":["Basic &amp; 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