{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:28:48Z","timestamp":1778866128728,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:p>Trimethoprim is predicted to inhibit\u00a0several thiamine transporters, including the primary thiamine intestinal absorptive transporter, ThTR\u20102, and the hepatic and renal organic cation transporters, OCT1, OCT2, and MATEs. To investigate the effect of trimethoprim on thiamine absorption, studies were conducted in cells, mice, and healthy volunteers and supported by use of real\u2010world data. In a randomized, crossover clinical study, seven healthy volunteers were given a single oral dose of thiamine or thiamine plus trimethoprim, followed by blood sampling. The thiamine area under the curve (AUC) increased with trimethoprim co\u2010administration (<jats:italic>P<\/jats:italic> value\u2009=\u20090.031). Similar results were seen in mice. Trimethoprim appeared to act on thiamine absorption through inhibition of hepatic OCT1 as evidenced from its ability to modulate levels of isobutyrylcarnitine and propionylcarnitine, OCT1 biomarkers identified from metabolomic analyses. Real\u2010world data further supported this finding, showing an association between trimethoprim use and higher levels of triglycerides, LDL cholesterol, and total cholesterol, consistent with OCT1 inhibition (<jats:italic>P<\/jats:italic> values: 2.2\u2009\u00d7\u200910<jats:sup>\u221216<\/jats:sup>, 5.75\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup>, and 5.82\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup>, respectively). These findings suggest that trimethoprim increases plasma levels of thiamine by inhibiting hepatic OCT1. Trimethoprim reduced urinary excretion and clearance of biomarkers for OCT2 and MATEs, consistent with inhibition of renal organic cation transporters. This inhibition did not appear to play a role in the observed increases in thiamine levels. This study highlights the potential for drug\u2010nutrient interactions involving transporters, in addition to transporters' established role in drug\u2013drug interactions.<\/jats:p>","DOI":"10.1002\/cpt.2932","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T05:55:22Z","timestamp":1683525322000},"page":"381-392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Effect of Trimethoprim on Thiamine Absorption: A <scp>Transporter\u2010Mediated Drug\u2010Nutrient<\/scp> Interaction"],"prefix":"10.1111","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0501-1804","authenticated-orcid":false,"given":"Bianca","family":"Vora","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Nutrition University of California Davis  Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8121-8746","authenticated-orcid":false,"given":"Sook Wah","family":"Yee","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim","family":"Trinh","sequence":"additional","affiliation":[{"name":"Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging Tufts University  Medford Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mina","family":"Azimi","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A. 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