{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T04:11:02Z","timestamp":1778299862719,"version":"3.51.4"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>\n                    Cinnamon (\n                    <jats:italic>Cinnamomum<\/jats:italic>\n                    spp.) is used as a culinary spice and dietary supplement. A major constituent, cinnamaldehyde, was previously shown to inactivate cytochrome P450 (CYP) 2A6 in\u00a0vitro. A mechanistic static model predicted an ~5\u2010fold increase in the AUC of the CYP2A6 substrates nicotine and letrozole. Accordingly, the effects of a well\u2010characterized cinnamon (\n                    <jats:italic>Cinnamomum verum<\/jats:italic>\n                    ) product on the pharmacokinetics of nicotine and letrozole were evaluated in 16 healthy, non\u2010nicotine using adults. They were administered a single dose of nicotine gum (2\u2009mg) or letrozole tablet (2.5\u2009mg) (baseline). After a sufficient washout (2\u201314\u2009days), they self\u2010administered\n                    <jats:italic>C. verum<\/jats:italic>\n                    (2\u2009g thrice daily) for 5 consecutive days. On Day 6, they were administered\n                    <jats:italic>C. verum<\/jats:italic>\n                    with nicotine or letrozole, followed by two more doses of\n                    <jats:italic>C. verum<\/jats:italic>\n                    (cinnamon exposure). Plasma was collected from 0 to 12 (nicotine) or 0\u2013240 (letrozole) hours. The geometric mean plasma concentration vs. time profile for both drugs was nearly superimposable in the presence vs. absence of\n                    <jats:italic>C. verum<\/jats:italic>\n                    . The geometric mean ratio (GMR) [90% confidence interval] of the AUC of nicotine and letrozole in the presence to absence of cinnamon was 0.98 [0.96\u20131.12] and 1.11 [0.98\u20131.24], respectively (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&gt;\u20090.16), indicating no interactions. Application of the \u201cslope approach\u201d involving the 3\u2010hydroxycotinine\u2010to\u2010cotinine ratio provided potential new mechanistic insight into CYP2A6 inhibition. The general lack of effect of a typical dosage of\n                    <jats:italic>C. verum<\/jats:italic>\n                    on the pharmacokinetics of nicotine and letrozole suggests that\n                    <jats:italic>C. verum<\/jats:italic>\n                    may be safe to consume with both drugs, as well as other CYP2A6 substrates.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70218","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T06:25:52Z","timestamp":1770013552000},"page":"1485-1493","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic Evaluation of a Cinnamon Product on\n                    <scp>CYP2A6<\/scp>\n                    Substrate Drugs: Application of a Novel Tool Involving the Nicotine Metabolite Ratio"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6159-039X","authenticated-orcid":false,"given":"Aiden\u2010Hung P.","family":"Nguyen","sequence":"first","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deena L.","family":"Hadi","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane WA USA"},{"name":"Center of Excellence for Natural Product Drug Interaction Research  Spokane WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2199-1029","authenticated-orcid":false,"given":"Daniel A.","family":"Todd","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of North Carolina at Greensboro  Greensboro North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Preston K.","family":"Manwill","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of North Carolina at Greensboro  Greensboro North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R.","family":"White","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew E.","family":"Layton","sequence":"additional","affiliation":[{"name":"Elson S. Floyd College of Medicine Washington State University  Spokane WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadja B.","family":"Cech","sequence":"additional","affiliation":[{"name":"Center of Excellence for Natural Product Drug Interaction Research  Spokane WA USA"},{"name":"Department of Chemistry and Biochemistry University of North Carolina at Greensboro  Greensboro North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth E.","family":"Thummel","sequence":"additional","affiliation":[{"name":"Center of Excellence for Natural Product Drug Interaction Research  Spokane WA USA"},{"name":"Department of Pharmaceutics, School of Pharmacy University of Washington  Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3331-1839","authenticated-orcid":false,"given":"Mary F.","family":"Paine","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane WA USA"},{"name":"Center of Excellence for Natural Product Drug Interaction Research  Spokane WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"e_1_2_10_1_1","first-page":"54","article-title":"US sales of herbal supplements increase 4.4% in 2023","volume":"141","author":"Smith T.","year":"2024","journal-title":"HerbalGram"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.9b01285"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-122113"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2009.01094.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201600013"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04777-1"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.067942"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.120.000087"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb971"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.3.1.51"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920007780866807"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.000547"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.076836"},{"key":"e_1_2_10_14_1","unstructured":"US Food and Drug Administration.M12 drug interaction studies: guidance for industry(2023)."},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1162"},{"key":"e_1_2_10_16_1","unstructured":"Bundesinstitut f\u00fcr Risikobewertung Cassia cinnamon with high coumarin contents to be consumed in moderation<https:\/\/www.bfr.bund.de\/en\/press_information\/2012\/26\/cassia_cinnamon_with_high_coumarin_contents_to_be_consumed_in_moderation\u2010131836.html> (2012)."},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13115"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14030620"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2107"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13884"},{"key":"e_1_2_10_21_1","volume-title":"Examining Intra\u2010Individual and Inter\u2010Individual Variability of Plasma Nicotine pk Parameters in E\u2010Vapor Use by Adult Cigarette Smokers in Three Studies","author":"Liang Q.","year":"2018"},{"key":"e_1_2_10_22_1","first-page":"419","article-title":"Bioequivalence study of two letrozole tablet formulations. 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