{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:31:39Z","timestamp":1791909099594,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T00:00:00Z","timestamp":1540425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:p>This study investigated the influence of the rate of nicotine metabolism, as indicated by the nicotine metabolite ratio (<jats:styled-content style=\"fixed-case\">NMR<\/jats:styled-content>), on tobacco dependence. We stratified 136 smokers on the basis of saliva<jats:styled-content style=\"fixed-case\">NMR<\/jats:styled-content>as fast (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>65) and slow (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>71) metabolizers. Two \u201cloading cigarettes\u201d were smoked after overnight, and a \u201creward cigarette\u201d was smoked after 6\u00a0hours of daytime, abstinence. Blood nicotine concentrations, expired carbon monoxide, withdrawal\/craving, and reward questionnaires were collected before\/after smoking and during daytime abstinence. Compared with slow metabolizers, fast metabolizers had a shorter nicotine elimination half\u2010life (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), lower plasma nicotine concentrations (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), and higher withdrawal\/craving scores (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) for most times during daytime abstinence, indicating that fast metabolizers are likely smoking more to relieve withdrawal symptoms (negative reinforcement). Reward\/satisfaction scores were similar in fast and slow metabolizers, suggesting that faster nicotine metabolism, assessed by<jats:styled-content style=\"fixed-case\">NMR,<\/jats:styled-content>is not associated with greater positive reinforcement.<jats:italic><jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>2A6<\/jats:italic>normal (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>82) and reduced (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>42) genotype predicted plasma nicotine concentrations but not withdrawal symptoms.<\/jats:p>","DOI":"10.1002\/cpt.1238","type":"journal-article","created":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T13:21:54Z","timestamp":1537622514000},"page":"641-651","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Effects of Nicotine Metabolic Rate on Withdrawal Symptoms and Response to Cigarette Smoking After Abstinence"],"prefix":"10.1111","volume":"105","author":[{"given":"Evangelia","family":"Liakoni","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology and Experimental Therapeutics Department of Medicine University of California, San Francisco San Francisco California USA"},{"name":"Clinical Pharmacology and Toxicology Department of General Internal Medicine Inselspital Bern University Hospital University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn C.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Westat Rockville Maryland USA"},{"name":"Center for Tobacco Control Research and Education University of California, San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon","family":"St. Helen","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Experimental Therapeutics Department of Medicine University of California, San Francisco San Francisco California USA"},{"name":"Center for Tobacco Control Research and Education University of California, San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Nardone","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Experimental Therapeutics Department of Medicine University of California, San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia A.","family":"Dempsey","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Experimental Therapeutics Department of Medicine University of California, San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel F.","family":"Tyndale","sequence":"additional","affiliation":[{"name":"Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health Toronto ON Canada"},{"name":"Departments of Pharmacology and Toxicology and Psychiatry University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2041-8124","authenticated-orcid":false,"given":"Neal L.","family":"Benowitz","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Experimental Therapeutics Department of Medicine University of California, San Francisco San Francisco California USA"},{"name":"Center for Tobacco Control Research and Education University of California, San Francisco San Francisco California USA"},{"name":"Department of Bioengineering and Therapeutic Sciences University of California, San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,25]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.48.113006.094742"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2004.02.011"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/30.6.386"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-08-0242"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-12-0236"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-3679"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2006.02.006"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.57"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2008.10.016"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.19"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(14)70294-2"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.336"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addbeh.2015.07.019"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.119"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/ntr\/ntv228"},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/S0022-3565(24)35227-9","article-title":"Ethnic differences in N\u2010glucuronidation of nicotine and cotinine","volume":"291","author":"Benowitz N.L.","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.280.2.152"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20698"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2006.11.012"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.037093"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm7040018"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwn301"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2006.01.008"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.016568"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/13556219871930"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1037\/1064-1297.5.2.137"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/14622200410001734067"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-111314-033712"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/tc.11.4.368"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/1462220031000158717"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/ntr\/ntp051"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-12-1234-T"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000222"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-200202000-00026"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/01213011-200502000-00007"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005498"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.1991.tb01879.x"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/ntr\/ntr072"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(00)00261-6"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-002-1176-1"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02311176"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1986.01800030107013"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1080\/14622200020032051"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addbeh.2006.06.028"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1037\/0022-3514.54.6.1063"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2010.12.012"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/bms.1200200503"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.15.156"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-11-0545"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1509693"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpt.1238","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1238","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.1238","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1238","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T20:01:30Z","timestamp":1752004890000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.1238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,25]]},"references-count":50,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1002\/cpt.1238"],"URL":"https:\/\/doi.org\/10.1002\/cpt.1238","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,25]]},"assertion":[{"value":"2018-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}