{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:18:37Z","timestamp":1789193917573,"version":"build-2803163510"},"reference-count":16,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,4,20]],"date-time":"2020-04-20T00:00:00Z","timestamp":1587340800000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The pharmacokinetics (PK), metabolism, excretion, mass balance, and tissue distribution of [<jats:sup>14<\/jats:sup>C]praliciguat were evaluated following oral administration of a 3\u2010mg\/kg dose in Sprague\u2010Dawley rats and in a quantitative whole\u2010body autoradiography (QWBA) study conducted in male Long\u2010Evans rats. Plasma <jats:italic>T<\/jats:italic><jats:sub>max<\/jats:sub> was 1\u00a0hour and the <jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub> of total plasma radioactivity was 23.7\u00a0hours. Unchanged praliciguat accounted for 87.4%, and a minor metabolite (<jats:italic>N<\/jats:italic>\u2010dealkylated\u2010praliciguat) accounted for 7.6% of the total radioactivity in plasma through 48\u00a0hours (AUC<jats:sub>0\u201048<\/jats:sub>). Tissues with the highest exposure ratios relative to plasma were liver, intestines, adrenal gland, and adipose, and those with the lowest values were seminal vesicle, blood, CNS tissues, lens of the eye, and bone. Most of the [<jats:sup>14<\/jats:sup>C]praliciguat\u2010derived radioactivity was excreted within 48\u00a0hours after oral administration. Mean cumulative recovery of the administered radioactivity in urine and feces over 168\u00a0hours was 3.7% and 95.7%, respectively. Unchanged praliciguat was not quantifiable in urine or bile of cannulated rats; however, based on the total radioactivity in these fluids, a minimum of approximately 82% of the orally administered dose was absorbed. [<jats:sup>14<\/jats:sup>C]Praliciguat was metabolized via oxidative and glucuronidation pathways and the most abundant metabolites recovered in bile were praliciguat\u2010glucuronide and hydroxy\u2010praliciguat\u2010glucuronide. These results indicate that praliciguat had rapid absorption, high bioavailability, extensive tissue distribution, and elimination primarily via hepatic metabolism.<\/jats:p>","DOI":"10.1002\/prp2.579","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T05:29:50Z","timestamp":1587446990000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pharmacokinetics, mass balance, tissue distribution, metabolism, and excretion of praliciguat, a clinical\u2010stage soluble guanylate cyclase stimulator in rats"],"prefix":"10.1002","volume":"8","author":[{"given":"Ali R.","family":"Banijamali","sequence":"first","affiliation":[{"name":"Department of Drug Metabolism and Pharmacokinetics Cyclerion Therapeutics Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew E.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Drug Metabolism and Pharmacokinetics Cyclerion Therapeutics Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Wakefield","sequence":"additional","affiliation":[{"name":"Department of Drug Metabolism and Pharmacokinetics Cyclerion Therapeutics Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6766-0885","authenticated-orcid":false,"given":"Peter","family":"Germano","sequence":"additional","affiliation":[{"name":"Department of Drug Metabolism and Pharmacokinetics Cyclerion Therapeutics Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy C.","family":"Barden","sequence":"additional","affiliation":[{"name":"Department of Drug Metabolism and Pharmacokinetics Cyclerion Therapeutics Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny V.","family":"Tobin","sequence":"additional","affiliation":[{"name":"Department of Drug Metabolism and Pharmacokinetics Cyclerion Therapeutics Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Department of Drug Metabolism and Pharmacokinetics Cyclerion Therapeutics Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime L.","family":"Masferrer","sequence":"additional","affiliation":[{"name":"Department of Drug Metabolism and Pharmacokinetics Cyclerion Therapeutics Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert T.","family":"Profy","sequence":"additional","affiliation":[{"name":"Department of Drug Metabolism and Pharmacokinetics Cyclerion Therapeutics Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark G.","family":"Currie","sequence":"additional","affiliation":[{"name":"Department of Drug Metabolism and Pharmacokinetics Cyclerion Therapeutics Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Todd Milne","sequence":"additional","affiliation":[{"name":"Department of Drug Metabolism and Pharmacokinetics Cyclerion Therapeutics Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0304264101"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2018_197"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-050410-100030"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2018.05.009"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209655"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209657"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.117.247429"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.627"},{"key":"e_1_2_9_10_1","first-page":"A19","article-title":"14\u2010Day study of praliciguat, a soluble guanylate cyclase stimulator, in patients with diabetes and hypertension","volume":"67","author":"Hanrahan JP","year":"2018","journal-title":"Diabetes"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1056-8719(02)00162-4"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/js970486q"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1444"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14137"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1821045116"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8235"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2337\/db18-1886-P"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprp2.579","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.579","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/prp2.579","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.579","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T06:41:41Z","timestamp":1694068901000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.579"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4]]},"references-count":16,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.1002\/prp2.579"],"URL":"https:\/\/doi.org\/10.1002\/prp2.579","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4]]},"assertion":[{"value":"2020-01-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00579"}}