{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:21:21Z","timestamp":1790785281464,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,6,6]],"date-time":"2017-06-06T00:00:00Z","timestamp":1496707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","award":["A15\u20100461"],"award-info":[{"award-number":["A15\u20100461"]}],"id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec><jats:title>AIM<\/jats:title><jats:p>The aim of the present study was to evaluate the effect of the proposed organic cation transporter (OCT) inhibitor daclatasvir on the pharmacokinetics and pharmacodynamics of the OCT substrate metformin.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>This was an open\u2010label, two\u2010period, randomized, crossover trial in 20 healthy subjects. Treatment A consisted of metformin and treatment B consisted of metformin\u00a0+\u00a0daclatasvir. Pharmacokinetic curves were recorded at steady\u2010state. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) were calculated for metformin area under the concentration\u2013time curve from 0\u00a0h to 12\u00a0h (AUC<jats:sub>0\u201312<\/jats:sub>), maximum plasma concentration (C<jats:sub>max<\/jats:sub>) and final plasma concentration (C<jats:sub>last<\/jats:sub>). An oral glucose tolerance test was performed, measuring insulin, glucose and lactate levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The GMRs (90% CI) of metformin AUC<jats:sub>0\u201312<\/jats:sub>, C<jats:sub>max<\/jats:sub> and C<jats:sub>last<\/jats:sub> (B <jats:italic>vs.<\/jats:italic> A) were 109% (102\u2013116%), 108% (101\u2013116%) and 112% (103\u2013122%). The geometric mean AUC<jats:sub>0\u20132<\/jats:sub> for insulin, glucose and lactate during treatments A and B were 84\u00a0h<jats:sup>.<\/jats:sup>mEl<jats:sup>\u20131<\/jats:sup> and 90\u00a0h<jats:sup>.<\/jats:sup>mEl<jats:sup>\u20131<\/jats:sup>, 13.6\u00a0h<jats:sup>.<\/jats:sup>mmol l<jats:sup>\u20131<\/jats:sup> and 13.4\u00a0h<jats:sup>.<\/jats:sup>mmol l<jats:sup>\u20131<\/jats:sup>, and 3.4\u00a0h<jats:sup>.<\/jats:sup>mmol l<jats:sup>\u20131<\/jats:sup> and 3.5\u00a0h<jats:sup>.<\/jats:sup>mmol l<jats:sup>\u20131<\/jats:sup>, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Bioequivalence analysis showed that daclatasvir does not influence the pharmacokinetics of metformin in healthy subjects. Pharmacodynamic parameters were also comparable between treatments.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13323","type":"journal-article","created":{"date-parts":[[2017,5,5]],"date-time":"2017-05-05T11:18:24Z","timestamp":1493983104000},"page":"2225-2234","source":"Crossref","is-referenced-by-count":8,"title":["Metformin and daclatasvir: absence of a pharmacokinetic\u2013pharmacodynamic drug interaction in healthy volunteers"],"prefix":"10.1111","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5694-9758","authenticated-orcid":false,"given":"Elise J.","family":"Smolders","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Radboud Institute for Health Sciences (RIHS) Radboud university medical center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Colbers","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Radboud Institute for Health Sciences (RIHS) Radboud university medical center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara T. 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