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In 3 separate studies, pharmacokinetic drug\u2013drug interactions (DDIs) potential was assessed when LCZ696 was coadministered with hydrochlorothiazide (HCTZ), amlodipine, or carvedilol. The studies used a open\u2010label, single\u2010sequence, 3\u2010period, crossover design in healthy subjects. Blood samples were collected to determine the pharmacokinetic parameters of LCZ696 analytes (AHU377, LBQ657, and valsartan), HCTZ, amlodipine, or carvedilol (R[+]\u2010 and S[\u2212]\u2010carvedilol) for statistical analysis. When coadministered LCZ696 with HCTZ, the 90% CIs of the geometric mean ratios of AUC<jats:sub>tau,ss<\/jats:sub> of HCTZ and that of LBQ657 were within a 0.80\u20131.25 interval, whereas HCTZ C<jats:sub>max,ss<\/jats:sub> decreased by 26%, LBQ657 C<jats:sub>max,ss<\/jats:sub> increased by 19%, and the AUC<jats:sub>tau,ss<\/jats:sub> and C<jats:sub>max,ss<\/jats:sub> of valsartan increased by 14% and 16%, respectively. Pharmacokinetics of amlodipine, R(+)\u2010 and S(\u2212)\u2010carvedilol, or LBQ657 were not altered after coadministration of LCZ696 with amlodipine or carvedilol. Coadministration of LCZ696 400\u2009mg once daily (qd) with HCTZ 25\u2009mg qd, amlodipine 10\u2009mg qd, or carvedilol 25\u2009mg twice a day (bid) had no clinically relevant pharmacokinetic drug\u2013drug interactions. LCZ696, HCTZ, amlodipine, and carvedilol were safe and well tolerated when given alone or concomitantly in the investigated studies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cpdd.183","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T04:48:53Z","timestamp":1423802933000},"page":"407-417","source":"Crossref","is-referenced-by-count":23,"title":["Pharmacokinetic drug\u2013drug interaction assessment between LCZ696, an angiotensin receptor neprilysin inhibitor, and hydrochlorothiazide, amlodipine, or carvedilol"],"prefix":"10.1002","volume":"4","author":[{"given":"Hsiu\u2010ling","family":"Hsiao","sequence":"first","affiliation":[{"name":"Novartis Institutes for Biomedical Research Novartis Pharmaceuticals Corporation East Hanover NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas Heiko","family":"Langenickel","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Greeley","sequence":"additional","affiliation":[{"name":"Oncology Clinical Pharmacology Novartis Pharmaceuticals Corporation East Hanover NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Roberts","sequence":"additional","affiliation":[{"name":"Oncology Clinical Pharmacology Novartis Pharmaceuticals Corporation East Hanover NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research Novartis Pharmaceuticals Corporation East Hanover NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parasar","family":"Pal","sequence":"additional","affiliation":[{"name":"Novartis Healthcare Pvt. 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