{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T06:23:51Z","timestamp":1777530231697,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T00:00:00Z","timestamp":1554940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The quaternary ammonium compound trospium chloride is poorly absorbed from 2 \u201cabsorption windows\u201d in the jejunum and cecum\/ascending colon, respectively. To confirm whether intestinal P\u2010glycoprotein (P\u2010gp) is involved, a 4\u2010period, crossover drug interaction study with trospium chloride after intravenous (2\u00a0mg) and oral administration (30\u00a0mg) without and after comedication of clarithromycin (500\u00a0mg), an inhibitor for P\u2010gp, was initiated in 12 healthy subjects. Pharmacokinetics of trospium was evaluated using gas chromatography\u2013mass spectrometry, noncompartmental evaluation, and pharmacokinetic modeling. Trospium chloride was poorly absorbed after oral administration (absolute bioavailability, \u223c8%\u201310%). About 30% of the bioavailable dose fraction was absorbed from the \u201cnarrow window\u201d. Comedication with clarithromycin increased steady\u2010state distribution volumes by \u223c27% (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.01). Bioavailability was not increased as hypothesized. The geometric mean ratios (90% confidence interval) for area under the plasma concentration\u2013time curve, maximum concentration, and renal clearance accounted for 0.75 (0.56\u20131.01), 0.64 (0.45\u20130.89), and 1.00 (0.90\u20131.13), respectively. The amount of trospium absorbed from the \u201cnarrow window\u201d was reduced in all subjects but from the \u201cwider window\u201d in only 9 of them. Bioavailability was strongly predicted by the maximum absorption rate of trospium in the distal \u201cwindow\u201d (rs<jats:sup>2<\/jats:sup>\u00a0=\u00a00.910, <jats:italic>P<\/jats:italic>\u00a0&lt; .0001). In conclusion, the P\u2010gp inhibitor clarithromycin significantly increases distribution volumes but not oral absorption of trospium. The amount absorbed from the \u201cnarrow window\u201d was lowered in all subjects. However, the extent of all influences seems not to be of clinical relevance.<\/jats:p>","DOI":"10.1002\/jcph.1421","type":"journal-article","created":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T04:02:28Z","timestamp":1555041748000},"page":"1319-1330","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effects of the P\u2010Glycoprotein Inhibitor Clarithromycin on the Pharmacokinetics of Intravenous and Oral Trospium Chloride: A 4\u2010Way Crossover Drug\u2010Drug Interaction Study in Healthy Subjects"],"prefix":"10.1002","volume":"59","author":[{"given":"Bayew Tsega","family":"Abebe","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Center of Drug Absorption and Transport (C_DAT) University of Greifswald  Greifswald Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of 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