{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T06:36:55Z","timestamp":1756190215139,"version":"3.37.3"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,5,31]],"date-time":"2017-05-31T00:00:00Z","timestamp":1496188800000},"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":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Tenapanor (RDX5791\/AZD1722), an inhibitor of gastrointestinal Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup> exchanger NHE3, is being evaluated for the treatment of patients with constipation\u2010predominant irritable bowel syndrome and the treatment of hyperphosphataemia in patients with chronic kidney disease on dialysis. By reducing intestinal H<jats:sup>+<\/jats:sup> secretion, inhibition of NHE3 by tenapanor could indirectly affect H<jats:sup>+<\/jats:sup>\u2010coupled transporter activity, leading to drug\u2013drug interactions. We investigated the effect of tenapanor on the activity of the H<jats:sup>+<\/jats:sup>\u2010coupled peptide transporter PepT1 via assessment of the pharmacokinetics of cefadroxil \u2013 a compound transported by PepT1 \u2013 in healthy volunteers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this open\u2010label, two\u2010period crossover, phase 1 study (NCT02140281), 28 volunteers received in random order: a single dose of cefadroxil 500 mg for 1 day; and tenapanor 15 mg twice daily over 4 days followed by single doses of both cefadroxil 500 mg and tenapanor 15 mg on day 5. There was a 4\u2010day washout between treatment periods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cefadroxil exposure was similar when administered alone or in combination with tenapanor {geometric least\u2010squares mean ratios [(cefadroxil\u00a0+\u00a0tenapanor)\/cefadroxil] (90% confidence interval): area under the concentration\u2013time curve 93.3 (90.6\u201396.0)%; maximum concentration in plasma 95.9 (89.8\u2013103)%}. Tenapanor treatment caused a softening of stool consistency and an increase in stool frequency, consistent with its expected pharmacodynamic effect. No safety concerns were identified and tenapanor was not detected in plasma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest that tenapanor 15 mg twice daily does not have a clinically relevant impact on the activity of the H<jats:sup>+<\/jats:sup>\u2010coupled transporter PepT1 in humans. This may guide future research on drug\u2013drug interactions involving NHE3 inhibitors.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13313","type":"journal-article","created":{"date-parts":[[2017,4,22]],"date-time":"2017-04-22T06:32:50Z","timestamp":1492842770000},"page":"2008-2014","source":"Crossref","is-referenced-by-count":10,"title":["Tenapanor administration and the activity of the H<sup>+<\/sup>\u2010coupled transporter PepT1 in healthy volunteers"],"prefix":"10.1111","volume":"83","author":[{"given":"Susanne","family":"Johansson","sequence":"first","affiliation":[{"name":"Quantitative Clinical Pharmacology, Innovative Medicines and Early Development Biotech Unit AstraZeneca  M\u00f6lndal Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9371-391X","authenticated-orcid":false,"given":"David P.","family":"Rosenbaum","sequence":"additional","affiliation":[{"name":"Ardelyx Inc.  Fremont CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"Palm","sequence":"additional","affiliation":[{"name":"Product Development, Pharmaceutical Technology &amp; Development, Operations AstraZeneca  M\u00f6lndal Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bergur","family":"Stefansson","sequence":"additional","affiliation":[{"name":"Cardiovascular Metabolic Diseases, Global Medicines Development AstraZeneca  M\u00f6lndal Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikael","family":"Knutsson","sequence":"additional","affiliation":[{"name":"Biometrics &amp; Information Sciences, Global Medicines Development AstraZeneca  M\u00f6lndal Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleanor A.","family":"Lisbon","sequence":"additional","affiliation":[{"name":"QuintilesIMS  Overland Park KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constanze","family":"Hilgendorf","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Pharmacokinetics, Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit AstraZeneca  M\u00f6lndal Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,5,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1037"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13355"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007790"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/969"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50429-X"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014030317"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2017.41"},{"key":"e_1_2_10_9_1","unstructured":"ClinicalTrials.gov. 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