{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:31:31Z","timestamp":1787563891717,"version":"build-2736575974"},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,9,22]],"date-time":"2019-09-22T00:00:00Z","timestamp":1569110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Dr. Pfleger Arzneimittel GmbH, Bamberg, Germany"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Trospium chloride, a muscarinic receptor blocker, is poorly absorbed with different rates from areas in the jejunum and the cecum\/ascending colon. To evaluate whether organic cation transporter (OCT) 1, OCT2 and multidrug and toxin extrusion (MATE) 1 and MATE2\u2010K are involved in pharmacokinetics, competitions with ranitidine, a probe inhibitor of the cation transporters, were evaluated in transfected HEK293 cells. Furthermore, a drug interaction study with trospium chloride after intravenous (2 mg) and oral dosing (30 mg) plus ranitidine (300 mg) was performed in 12 healthy subjects and evaluated by noncompartmental analysis and population pharmacokinetic modeling. Ranitidine inhibited OCT1, OCT2, MATE1, and MATE2\u2010K with half maximal inhibitory concentration values of 186\u00a0\u00b1\u00a025 \u00b5M, 482\u00a0\u00b1\u00a0105 \u00b5M, 134\u00a0\u00b1\u00a037 \u00b5M, and 35\u00a0\u00b1\u00a011 \u00b5M, respectively. In contrast to our hypothesis, coadministration of ranitidine did not significantly decrease oral absorption of trospium. Instead, renal clearance was lowered by \u223c15% (530\u00a0\u00b1\u00a099 vs 460\u00a0\u00b1\u00a0120 mL\/min;\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a0.05). It is possible that ranitidine was not available in competitive concentrations at the major colonic absorption site, as the inhibitor is absorbed in the small intestine and undergoes degradation by microbiota. The renal effects apparently result from inhibition of MATE1 and\/or MATE2\u2010K by ranitidine as predicted by in vitro to in vivo extrapolation. However, all pharmacokinetic changes were not of clinical relevance for the drug with highly variable pharmacokinetics. Intravenous trospium significantly lowered mean absorption time and relative bioavailability of ranitidine, which was most likely caused by muscarinic receptor blocking effects on intestinal motility and water turnover.\n                  <\/jats:p>","DOI":"10.1002\/jcph.1523","type":"journal-article","created":{"date-parts":[[2019,9,22]],"date-time":"2019-09-22T08:59:03Z","timestamp":1569142743000},"page":"312-323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Pharmacokinetic Drug\u2010Drug Interactions Between Trospium Chloride and Ranitidine Substrates of Organic Cation Transporters in Healthy Human Subjects"],"prefix":"10.1002","volume":"60","author":[{"given":"Bayew Tsega","family":"Abebe","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Center of Drug Absorption and Transport (C_DAT) University Medicine of Greifswald  Greifswald 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