{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:25:59Z","timestamp":1790753159425,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,6,21]],"date-time":"2018-06-21T00:00:00Z","timestamp":1529539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Previous pharmacokinetic characterization of a transporter probe cocktail containing digoxin (P\u2010gp), furosemide (OAT1, OAT3), metformin (OCT2, MATE1, MATE2\u2010K) and rosuvastatin (OATP1B1, OATP1B3, BCRP) in healthy subjects showed increases in rosuvastatin systemic exposure compared to rosuvastatin alone. In this trial, the doses of metformin and furosemide as putative perpetrators were reduced to eliminate their drug\u2013drug interaction (DDI) with rosuvastatin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a randomized, open\u2010label, single\u2010centre, five\u2010treatment, five\u2010period crossover trial, 30 healthy male subjects received as reference treatments separately 0.25\u00a0mg digoxin, 1\u00a0mg furosemide, 10\u00a0mg metformin and 10\u00a0mg rosuvastatin, and as test treatment all four drugs administered together as a cocktail. Primary pharmacokinetic endpoints were AUC\n                      <jats:sub>0\u2010tz<\/jats:sub>\n                      (area under the plasma concentration\u2013time curve from time zero to the last quantifiable concentration) and\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      (maximum plasma concentration) of each probe drug.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Geometric mean ratios and 90% confidence intervals of test (cocktail) to reference (single drug) for AUC\n                      <jats:sub>0\u2010tz<\/jats:sub>\n                      were 96.4% (88.2\u2013105.3%) for digoxin, 102.6% (93.8\u2013112.3%) for furosemide, 97.5% (93.5\u2013101.6%) for metformin and 105.0% (96.4\u2013114.4%) for rosuvastatin, indicating lack of interaction. The same analysis for\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      and for pharmacokinetic parameters of urinary excretion of all cocktail components also indicated no DDI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Digoxin (0.25\u00a0mg), furosemide (1\u00a0mg), metformin (10\u00a0mg) and rosuvastatin (10\u00a0mg) exhibit no mutual pharmacokinetic interactions and are well tolerated administered as a cocktail. The cocktail is thus optimized and has the potential to be used as a screening tool for clinical investigation of transporter\u2010mediated DDI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.13609","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T15:08:13Z","timestamp":1523977693000},"page":"1941-1949","source":"Crossref","is-referenced-by-count":45,"title":["Optimization of a drug transporter probe cocktail: potential screening tool for transporter\u2010mediated drug\u2013drug interactions"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0144-0895","authenticated-orcid":false,"given":"Peter","family":"Stopfer","sequence":"first","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Birkendorfer Str. 65 88397 Biberach an der Riss Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Giessmann","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Birkendorfer Str. 65 88397 Biberach an der Riss Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Hohl","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Birkendorfer Str. 65 88397 Biberach an der Riss Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Hutzel","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Birkendorfer Str. 65 88397 Biberach an der Riss Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Birkendorfer Str. 65 88397 Biberach an der Riss Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar","family":"Gansser","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Birkendorfer Str. 65 88397 Biberach an der Riss Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Ishiguro","sequence":"additional","affiliation":[{"name":"Kobe Pharma Research Institute Nippon Boehringer Ingelheim Co. Ltd.  Chuo\u2010ku Kobe City Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell E.","family":"Taub","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals Inc.  900 Ridgebury Road Ridgefield CT 06877 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Sharma","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. 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