{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:51:00Z","timestamp":1791827460672,"version":"4.3.4"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Drug Metab Pharmacokinet"],"DOI":"10.1007\/s13318-026-01041-x","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:27:08Z","timestamp":1791826028000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Model-Based Evaluation of the Warfarin\u2013Sulfamethoxazole Drug\u2013Drug Interaction"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7712-5714","authenticated-orcid":false,"given":"Koki","family":"Takeda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinori","family":"Hirai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kokoha","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayu","family":"Sugioka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhito","family":"Shibata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"1041_CR1","doi-asserted-by":"publisher","unstructured":"Van Gelder IC, Rienstra M, Bunting KV, Casado-Arroyo R, Caso V, Crijns HJGM, et al. 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): Developed by the task force for the management of atrial fibrillation of the European Society of Cardiology (ESC), with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Endorsed by the European Stroke Organisation (ESO). Eur Heart J. 2024;45(36):314\u2013414. https:\/\/doi.org\/10.1093\/eurheartj\/ehae176","DOI":"10.1093\/eurheartj\/ehae176"},{"key":"1041_CR2","unstructured":"Shikdar S, Vashisht R, Zubair M, Bhattacharya PT. International normalized ratio: assessment, monitoring, and clinical implications. In: StatPearls [Internet]. Treasure Island: StatPearls Publishing; [updated 2026 Jan; cited 2026 Aug 8]."},{"issue":"10","key":"1041_CR3","doi-asserted-by":"publisher","first-page":"2102","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.04.030","volume":"26","author":"T Hirano","year":"2017","unstructured":"Hirano T, Kaneko H, Mishina S, Wang F, Morita S. Suboptimal anticoagulant management in Japanese patients with nonvalvular atrial fibrillation receiving warfarin for stroke prevention. J Stroke Cerebrovasc Dis. 2017;26(10):2102\u201310. https:\/\/doi.org\/10.1016\/j.jstrokecerebrovasdis.2017.04.030.","journal-title":"J Stroke Cerebrovasc Dis"},{"issue":"1","key":"1041_CR4","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1161\/CIR.0000000000001193","volume":"83","author":"JA Joglar","year":"2023","unstructured":"Joglar JA, Chung MK, Armbruster AL, Benjamin EJ, Chyou JY, Cronin EM, et al. 2023 ACC\/AHA\/ACCP\/HRS guideline for the diagnosis and management of atrial fibrillation: a report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2023;83(1):109\u2013279. https:\/\/doi.org\/10.1161\/CIR.0000000000001193.","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"1041_CR5","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s11239-013-0978-9","volume":"38","author":"R Saito","year":"2014","unstructured":"Saito R, Takeda K, Yamamoto K, Nakagawa A, Aoki H, Fujibayashi K, et al. Nutri-pharmacogenomics of warfarin anticoagulation therapy: VKORC1 genotype-dependent influence of dietary vitamin K intake. J Thromb Thrombolysis. 2014;38(1):105\u201314. https:\/\/doi.org\/10.1007\/s11239-013-0978-9.","journal-title":"J Thromb Thrombolysis"},{"key":"1041_CR6","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1007\/s11239-013-0978-9","volume":"165","author":"AM Holbrook","year":"2005","unstructured":"Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005;165:1095\u2013106. https:\/\/doi.org\/10.1007\/s11239-013-0978-9.","journal-title":"Arch Intern Med"},{"issue":"6","key":"1041_CR7","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1111\/j.1365-2125.2006.02589.x","volume":"61","author":"D Ouellet","year":"2006","unstructured":"Ouellet D, Bramson C, Carvajal\u2010Gonzalez S, Roman D, Randinitis E, Remmers A, et al. Effects of lasofoxifene on the pharmacokinetics and pharmacodynamics of single-dose warfarin. Br J Clin Pharmacol. 2006;61(6):741\u20135. https:\/\/doi.org\/10.1111\/j.1365-2125.2006.02589.x.","journal-title":"Br J Clin Pharmacol"},{"issue":"6","key":"1041_CR8","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.121.007956","volume":"15","author":"PL Mar","year":"2022","unstructured":"Mar PL, Gopinathannair R, Gengler BE, Chung MK, Perez A, Dukes J, et al. Drug Interactions affecting oral anticoagulant use. Circ Arrhythm Electrophysiol. 2022;15(6):e007956. https:\/\/doi.org\/10.1161\/CIRCEP.121.007956.","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"1041_CR9","unstructured":"BACTRIM (sulfamethoxazole and trimethoprim) tablet [package insert]. Cranbury: Sun Pharmaceutical Industries, 2024. https:\/\/dailymed.nlm.nih.gov\/dailymed\/drugInfo.cfm?setid=f59d0c04-9c66-4d53-a0e1-cb55570deb62. Accessed 8 Aug 2026."},{"issue":"3","key":"1041_CR10","doi-asserted-by":"publisher","first-page":"227","DOI":"10.4140\/tcp.n.2009.227","volume":"24","author":"L Thi","year":"2009","unstructured":"Thi L, Shaw D, Bird J. Warfarin potentiation: a review of the \u201cFAB-4\u201d significant drug interactions. Consult Pharm. 2009;24(3):227\u201330. https:\/\/doi.org\/10.4140\/tcp.n.2009.227.","journal-title":"Consult Pharm"},{"issue":"9","key":"1041_CR11","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1016\/j.lfs.2004.02.020","volume":"75","author":"T Sugiyama","year":"2004","unstructured":"Sugiyama T, Kubota Y, Shinozuka K, Yamada S, Wu J, Umegaki K. Ginkgo biloba extract modifies hypoglycemic action of tolbutamide via hepatic cytochrome P450 mediated mechanism in aged rats. Life Sci. 2004;75(9):1113\u201322. https:\/\/doi.org\/10.1016\/j.lfs.2004.02.020.","journal-title":"Life Sci"},{"issue":"3","key":"1041_CR12","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/S0090-9556(25)06552-3","volume":"23","author":"AE Cribb","year":"1995","unstructured":"Cribb AE, Spielberg SP, Griffin GP. N4-hydroxylation of sulfamethoxazole by cytochrome P450 of the cytochrome P4502C subfamily and reduction of sulfamethoxazole hydroxylamine in human and rat hepatic microsomes. Drug Metab Dispos. 1995;23(3):406\u201314.","journal-title":"Drug Metab Dispos"},{"key":"1041_CR13","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1124\/dmd.115.066597","volume":"43","author":"LJ Haupt","year":"2015","unstructured":"Haupt LJ, Kazmi F, Ogilvie BW, Buckley DB, Smith BD, Leatherman S, et al. The reliability of estimating Ki values for direct, reversible inhibition of cytochrome P450 enzymes from corresponding IC50 values: a retrospective analysis of 343 experiments. Drug Metab Dispos. 2015;43:1744\u201350. https:\/\/doi.org\/10.1124\/dmd.115.066597.","journal-title":"Drug Metab Dispos"},{"key":"1041_CR14","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-019-2436-5","volume":"19","author":"M Alnaqeeb","year":"2019","unstructured":"Alnaqeeb M, Mansor KA, Mallah EM, Ghanim BY, Idkaidek N, Qinna NA. Critical pharmacokinetic and pharmacodynamic drug-herb interactions in rats between warfarin and pomegranate peel or guava leaves extracts. BMC Complement Altern Med. 2019;19:29. https:\/\/doi.org\/10.1186\/s12906-019-2436-5.","journal-title":"BMC Complement Altern Med"},{"key":"1041_CR15","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/clpt.2008.150","volume":"84","author":"H Schelleman","year":"2008","unstructured":"Schelleman H, Bilker WB, Brensinger CM, Han X, Kimmel SE, Hennessy S. Warfarin with fluoroquinolones, sulfonamides, or azole antifungals: interactions and the risk of hospitalization for gastrointestinal bleeding. Clin Pharmacol Ther. 2008;84:581\u20138. https:\/\/doi.org\/10.1038\/clpt.2008.150.","journal-title":"Clin Pharmacol Ther"},{"issue":"2","key":"1041_CR16","doi-asserted-by":"publisher","DOI":"10.1093\/rap\/rkaa029","volume":"4","author":"M Utsunomiya","year":"2020","unstructured":"Utsunomiya M, Dobashi H, Odani T, Saito K, Yokogawa N, Nagasaka K, et al. An open-label, randomized controlled trial of sulfamethoxazole\u2013trimethoprim for Pneumocystis prophylaxis: results of 52-week follow-up. Rheumatol Adv Pract. 2020;4(2):rkaa029. https:\/\/doi.org\/10.1093\/rap\/rkaa029.","journal-title":"Rheumatol Adv Pract"},{"issue":"2","key":"1041_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiac.2024.10.005","volume":"31","author":"K Takeda","year":"2025","unstructured":"Takeda K, Okada A, Sera S, Oishi T, Nagai N. Efficacy and safety of a low-dose sulfamethoxazole\/trimethoprim regimen in preventing pneumocystis pneumonia: a retrospective study using a large-scale electronic medical record database. J Infect Chemother. 2025;31(2):102537. https:\/\/doi.org\/10.1016\/j.jiac.2024.10.005.","journal-title":"J Infect Chemother"},{"issue":"6","key":"1041_CR18","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1016\/j.jmii.2017.07.007","volume":"51","author":"K Nakashima","year":"2018","unstructured":"Nakashima K, Aoshima M, Nakashita T, Hara M, Otsuki A, Noma S, et al. Low-dose trimethoprim-sulfamethoxazole treatment for pneumocystis pneumonia in non-human immunodeficiency virus-infected immunocompromised patients: a single-center retrospective observational cohort study. J Microbiol Immunol Infect. 2018;51(6):810\u201320. https:\/\/doi.org\/10.1016\/j.jmii.2017.07.007.","journal-title":"J Microbiol Immunol Infect"},{"issue":"9","key":"1041_CR19","first-page":"558","volume":"99","author":"M Carpenter","year":"2019","unstructured":"Carpenter M, Berry H, Pelletier AL. Clinically relevant drug\u2013drug interactions in primary care. Am Fam Physician. 2019;99(9):558\u201364.","journal-title":"Am Fam Physician"},{"issue":"1","key":"1041_CR20","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1007\/s11239-017-1497-x","volume":"44","author":"A Powers","year":"2017","unstructured":"Powers A, Loesch EB, Weiland A, Fioravanti N, Lucius D. Preemptive warfarin dose reduction after initiation of sulfamethoxazole-trimethoprim or metronidazole. J Thromb Thrombolysis. 2017;44(1):88\u201393. https:\/\/doi.org\/10.1007\/s11239-017-1497-x.","journal-title":"J Thromb Thrombolysis"},{"issue":"1","key":"1041_CR21","first-page":"106","volume":"47","author":"YC Shen","year":"2016","unstructured":"Shen YC, Xiang J, Liang MZ, Yu Q, Nan F, Qin YP. Determination of Warfarin Enantiomers in Human Plasma with HPLC-MS\/MS. Sichuan Da Xue Xue Bao Yi Xue Ban. 2016;47(1):106\u201310.","journal-title":"Sichuan Da Xue Xue Bao Yi Xue Ban."},{"key":"1041_CR22","unstructured":"US Department of Agriculture, Food Safety and Inspection Service. CLG-SUL 4.01: Quantitation and Confirmation of Sulfonamides by LC-MS\/MS. Cranbury: USDA Food Safety and Inspection Service. 2011. https:\/\/nucleus.iaea.org\/sites\/fcris\/Shared%20Documents\/SOP\/CLG_SUL_4_01.pdf_2011.pdf. Accessed 8 Aug 2026."},{"key":"1041_CR23","unstructured":"European Medicines Agency (EMA). Guideline on bioanalytical method validation. London: European Medicines Agency. 2011. https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-bioanalytical-method-validation_en.pdf. Accessed 8 Aug 2026."},{"key":"1041_CR24","unstructured":"U.S. Food and Drug Administration. estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. Rockville: Food and Drug Administration. 2005. https:\/\/www.fda.gov\/media\/72309\/download. Accessed 8 Aug 2026."},{"issue":"8","key":"1041_CR25","doi-asserted-by":"publisher","first-page":"731","DOI":"10.3109\/00498254.2012.661099","volume":"42","author":"A Zacha\u0159ov\u00e1","year":"2012","unstructured":"Zacha\u0159ov\u00e1 A, \u0160iller M, \u0160pi\u010d\u00e1kov\u00e1 A, Anzenbacherov\u00e1 E, \u0160kottov\u00e1 N, Anzenbacher P, et al. Rosuvastatin suppresses the liver microsomal CYP2C11 and CYP2C6 expression in male Wistar rats. Xenobiotica. 2012;42(8):731\u20136. https:\/\/doi.org\/10.3109\/00498254.2012.661099.","journal-title":"Xenobiotica"},{"issue":"6","key":"1041_CR26","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/s0002-9343(00)00545-3","volume":"109","author":"BF Gage","year":"2000","unstructured":"Gage BF, Fihn SD, White RH. Management and dosing of warfarin therapy. Am J Med. 2000;109(6):481\u20138. https:\/\/doi.org\/10.1016\/s0002-9343(00)00545-3.","journal-title":"Am J Med"},{"key":"1041_CR27","unstructured":"National Library of Medicine (US). Warfarin sodium tablet [Internet]. DailyMed; 2025. https:\/\/dailymed.nlm.nih.gov\/dailymed\/drugInfo.cfm?setid=ba8b4ead-d080-91e7-e053-2995a90a82fe. Accessed 9 June 2026."},{"key":"1041_CR28","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/B978-0-12-417205-0.00023-7","volume-title":"The practice of medicinal chemistry","author":"K Boussery","year":"2015","unstructured":"Boussery K, Belpaire FM, Van de Voorde J. Physiological aspects determining the pharmacokinetic properties of drugs. In: Wermuth CG, Aldous D, Raboisson P, Rognan D, editors. The practice of medicinal chemistry. 4th ed. London: Academic Press; 2015. p. 539\u201359. https:\/\/doi.org\/10.1016\/B978-0-12-417205-0.00023-7.","edition":"4th ed"},{"issue":"5","key":"1041_CR29","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1111\/j.1365-2125.2012.04259.x","volume":"74","author":"BP Jensen","year":"2012","unstructured":"Jensen BP, Chin PK, Roberts RL, Begg EJ. Influence of adult age on the total and free clearance and protein binding of (R)- and (S)-warfarin. Br J Clin Pharmacol. 2012;74(5):797\u2013805. https:\/\/doi.org\/10.1111\/j.1365-2125.2012.04259.x.","journal-title":"Br J Clin Pharmacol"},{"issue":"3","key":"1041_CR30","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1111\/bcp.15967","volume":"90","author":"T Hirai","year":"2024","unstructured":"Hirai T, Aoyama T, Tsuji Y, Itoh T, Matsumoto Y, Iwamoto T. Kinetic\u2013pharmacodynamic model of warfarin for prothrombin time\u2013international normalized ratio in Japanese patients. Br J Clin Pharmacol. 2024;90(3):828\u201336. https:\/\/doi.org\/10.1111\/bcp.15967.","journal-title":"Br J Clin Pharmacol"},{"issue":"4","key":"1041_CR31","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1111\/bcp.13157","volume":"83","author":"L Xue","year":"2017","unstructured":"Xue L, Holford N, Ding XL, Shen ZY, Huang CR, Zhang H, et al. Theory-based pharmacokinetics and pharmacodynamics of S- and R-warfarin and effects on international normalized ratio: influence of body size, composition and genotype in cardiac surgery patients. Br J Clin Pharmacol. 2017;83(4):823\u201335. https:\/\/doi.org\/10.1111\/bcp.13157.","journal-title":"Br J Clin Pharmacol"},{"issue":"11","key":"1041_CR32","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1007\/s00228-017-2316-1","volume":"73","author":"T Hirai","year":"2017","unstructured":"Hirai T, Hamada Y, Geka Y, Kuwana S, Hirai K, Ishibashi M, et al. A retrospective study on the risk factors for bleeding events in warfarin therapy, focusing on renal function. Eur J Clin Pharmacol. 2017;73(11):1491\u20137. https:\/\/doi.org\/10.1007\/s00228-017-2316-1.","journal-title":"Eur J Clin Pharmacol"}],"container-title":["European Journal of Drug Metabolism and Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13318-026-01041-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13318-026-01041-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13318-026-01041-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:27:10Z","timestamp":1791826030000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13318-026-01041-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,12]]},"references-count":32,"alternative-id":["1041"],"URL":"https:\/\/doi.org\/10.1007\/s13318-026-01041-x","relation":{},"ISSN":["0378-7966","2107-0180"],"issn-type":[{"value":"0378-7966","type":"print"},{"value":"2107-0180","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,12]]},"assertion":[{"value":"24 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All authors declare that they have no conflicts of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal experimental procedures were approved by the institutional review board (Y24-004) and conducted following the Guidelines for Animal Experimentation of Doshisha Women's College of Liberal Arts.","order":2,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":4,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}}]}}