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The potential for a drug\u2013drug interaction was explored in two phase 1 clinical studies in subjects with T2DM to evaluate the pharmacokinetics and safety of metformin 1000\u2009mg BID when administered with ranolazine 1000\u2009mg BID (<jats:italic>Study 1<\/jats:italic>, N\u2009=\u200928) or ranolazine 500\u2009mg BID (<jats:italic>Study 2<\/jats:italic>, N\u2009=\u200925) as compared to metformin alone. Co\u2010administration of ranolazine 1000\u2009mg BID with metformin 1000\u2009mg BID resulted in 1.53\u2010 and 1.79\u2010fold increases in steady\u2010state metformin C<jats:sub>max<\/jats:sub> and AUC<jats:sub>tau<\/jats:sub>, respectively; co\u2010administration of ranolazine 500\u2009mg BID with metformin 1000\u2009mg BID resulted in 1.22\u2010 and 1.37\u2010fold increases in steady\u2010state metformin C<jats:sub>max<\/jats:sub> and AUC<jats:sub>tau<\/jats:sub>, respectively. Co\u2010administration of ranolazine and metformin was well tolerated in these T2DM subjects, with no serious adverse events or drug\u2010related adverse events leading to discontinuation. The most common adverse events were nausea, diarrhea, and dizziness. These findings are consistent with a dose\u2010related interaction between ranolazine and metformin, and suggest that a dose adjustment of metformin may not be required with ranolazine 500\u2009mg BID; whereas, the metformin dose should not exceed 1700\u2009mg of total daily dose when using ranolazine 1000\u2009mg BID.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cpdd.174","type":"journal-article","created":{"date-parts":[[2014,11,25]],"date-time":"2014-11-25T09:55:47Z","timestamp":1416909347000},"page":"121-129","source":"Crossref","is-referenced-by-count":27,"title":["Pharmacokinetic drug\u2013drug interaction study of ranolazine and metformin in subjects with type 2 diabetes mellitus"],"prefix":"10.1002","volume":"4","author":[{"given":"Julia","family":"Zack","sequence":"first","affiliation":[{"name":"Gilead Sciences, Inc. Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jolene","family":"Berg","sequence":"additional","affiliation":[{"name":"DaVita Clinical Research Minneapolis MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Juan","sequence":"additional","affiliation":[{"name":"SeaView Research, Inc. Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Pannacciulli","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martine","family":"Allard","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mildred","family":"Gottwald","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. 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