{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:17:29Z","timestamp":1762507049188,"version":"3.41.0"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,3,16]],"date-time":"2017-03-16T00:00:00Z","timestamp":1489622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tenapanor (RDX5791, AZD1722) is an inhibitor of sodium\/hydrogen exchanger isoform 3 in development for the treatment of constipation\u2010predominant irritable bowel syndrome and the treatment of hyperphosphatemia in patients with chronic kidney disease on dialysis. We aimed to investigate whether tenapanor inhibits or induces cytochrome P450s (CYPs). In vitro experiments assessing the potential of tenapanor to affect various CYPs indicated that it could inhibit CYP3A4\/5 (IC<jats:sub>50<\/jats:sub>0.4\u20100.7 \u03bcM). An open\u2010label, phase 1 clinical study (NCT02140268) evaluated the pharmacokinetics of the CYP3A4 substrate midazolam when administered with and without tenapanor. Healthy volunteers received a single oral dose of midazolam 7.5\u00a0mg on day 1 followed by tenapanor 15\u00a0mg twice daily on days 2 to 15, with an additional single 7.5\u2010mg midazolam dose coadministered on day 15. Midazolam exposure was similar whether it was administered alone or with tenapanor (geometric least\u2010squares mean ratio [90%CI] for [midazolam + tenapanor]\/midazolam: area under the concentration\u2010time curve, 107% [101% to 113%]; C<jats:sub>max<\/jats:sub>104% [89.6% to 122%]). Findings were similar for metabolites of midazolam. These results indicate that tenapanor 15\u00a0mg twice daily does not have a clinically relevant impact on CYP3A4 in humans and suggest that tenapanor can be coadministered with CYP3A4\u2010metabolized drugs without affecting their exposure.<\/jats:p>","DOI":"10.1002\/cpdd.346","type":"journal-article","created":{"date-parts":[[2017,3,16]],"date-time":"2017-03-16T17:36:36Z","timestamp":1489685796000},"page":"466-475","source":"Crossref","is-referenced-by-count":10,"title":["Effects of Tenapanor on Cytochrome P450\u2010Mediated Drug\u2010Drug Interactions"],"prefix":"10.1002","volume":"6","author":[{"given":"Susanne","family":"Johansson","sequence":"first","affiliation":[{"name":"AstraZeneca Gothenburg M\u00f6lndal Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David P.","family":"Rosenbaum","sequence":"additional","affiliation":[{"name":"Ardelyx Inc., Fremont CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Ahlqvist","sequence":"additional","affiliation":[{"name":"AstraZeneca Gothenburg M\u00f6lndal Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Rollison","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikael","family":"Knutsson","sequence":"additional","affiliation":[{"name":"AstraZeneca Gothenburg M\u00f6lndal Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bergur","family":"Stefansson","sequence":"additional","affiliation":[{"name":"AstraZeneca Gothenburg M\u00f6lndal Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Elebring","sequence":"additional","affiliation":[{"name":"AstraZeneca Gothenburg M\u00f6lndal Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-008-0579-1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50428-8"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50429-X"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007790"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-016-1302-8"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014030317"},{"key":"e_1_2_8_8_1","first-page":"72A","article-title":"Tenapanor, a minimally absorbed NHE3 inhibitor, reduces dietary phosphorus absorption in healthy volunteers","volume":"25","author":"Rosenbaum D","year":"2014","journal-title":"J Am Soc Nephrol."},{"journal-title":"Am J Gastroenterol.","article-title":"Tenapanor treatment of patients with constipation-predominant irritable bowel syndrome: a phase 2, randomized, placebo-controlled efficacy and safety trial","author":"Chey WD","key":"e_1_2_8_9_1"},{"key":"e_1_2_8_10_1","unstructured":"ClinicalTrials.gov. A 12\u2010week study with a 4\u2010week randomized withdrawal period to evaluate the efficacy and safety of tenapanor for the treatment of IBS\u2010C (T3MPO\u20101).https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02621892. Accessed July 11 2016."},{"key":"e_1_2_8_11_1","unstructured":"ClinicalTrials.gov. A 26\u2010week study to evaluate the efficacy and safety of tenapanor in IBS\u2010C (T3MPO\u20102).https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02686138. Accessed June 1 2016."},{"journal-title":"J Am Soc Nephrol","article-title":"Effect of tenapanor on serum phosphate in patients receiving hemodialysis [published online ahead of print 2017]","author":"Block GA","key":"e_1_2_8_12_1"},{"key":"e_1_2_8_13_1","unstructured":"ClinicalTrials.gov. An 8\u2010week study to evaluate tenapanor in the treatment of hyperphosphatemia in end\u2010stage renal disease patients on hemodialysis (ESRD\u2010HD).https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02675998. Accessed June 28 2016."},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.09050815"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1211\/jpp.61.05.0002"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/S0090-9556(24)15229-4","article-title":"Characterization of human small intestinal cytochromes P\u2010450","volume":"27","author":"Zhang QY","year":"1999","journal-title":"Drug Metab Dispos."},{"key":"e_1_2_8_17_1","unstructured":"U.S. Food and Drug Administration.Guidance for industry: drug interaction studies\u2014study design data analysis implications for dosing and labeling recommendations. 2012.http:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/UCM292362.pdf. Accessed April 30 2015."},{"key":"e_1_2_8_18_1","unstructured":"European Medicines Agency.Guideline on the investigation of drug interactions. 2012.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2012\/07\/WC500129606.pdf. Accessed April 30 2015."},{"key":"e_1_2_8_19_1","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1124\/dmd.105.005173","article-title":"Simultaneous measurement of 23 isoforms from the human cytochrome P450 families 1 to 3 by quantitative reverse transcriptase\u2010polymerase chain reaction","volume":"33","author":"Girault I","year":"2005","journal-title":"Drug Metab Dispos."},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365529709011203"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2006.04.006"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.040931"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpdd.346","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.346","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T23:35:52Z","timestamp":1750116952000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,16]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1002\/cpdd.346"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.346","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"type":"print","value":"2160-763X"},{"type":"electronic","value":"2160-7648"}],"subject":[],"published":{"date-parts":[[2017,3,16]]}}}