{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T06:53:32Z","timestamp":1781765612033,"version":"3.54.5"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373938"],"award-info":[{"award-number":["82373938"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204585"],"award-info":[{"award-number":["82204585"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFF1202600"],"award-info":[{"award-number":["2022YFF1202600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    TPN729 is an oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction. Although several studies have investigated TPN729 metabolism, quantitative data delineating the involvement of primary excretion pathways and the fraction of each metabolic pathway are limited. This study utilized radioisotope tracing methods to examine the pharmacokinetics, mass balance, and metabolism of [\n                    <jats:sup>14<\/jats:sup>\n                    C]TPN729 (100\u2009\u03bcCi) after a single oral administration of 50\u2009mg in healthy male Chinese participants. TPN729 was rapidly absorbed, with a time to peak concentration (\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ) of 1.58\u2009h, suggesting that the peak plasma concentration was achieved shortly after oral administration. The elimination half\u2010life (\n                    <jats:italic>t<\/jats:italic>\n                    <jats:sub>1\/2<\/jats:sub>\n                    ) in plasma was 11.3\u2009h, indicating that the drug was eliminated from the body at a relatively slow rate. The ratio of total drug\u2010related chemicals in whole blood to plasma was 0.613, indicating preferential distribution in plasma. Mass balance measurements revealed that 95.7% of the radiolabeled chemical was excreted 192\u2009h after administration predominantly through feces (78.5%) rather than urine (17.2%). This study identified 17 metabolites in plasma, urine, and feces. All metabolites were phase I metabolites and were mainly generated through dealkylation and oxidation. These findings elucidate the metabolic pathway and clearance mechanisms of TPN729 in humans.\n                  <\/jats:p>","DOI":"10.1002\/bmc.70495","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T13:10:00Z","timestamp":1779801000000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics, Mass Balance, and Metabolism of [\n                    <sup>14<\/sup>\n                    C]TPN729, a Selective and Potent Phosphodiesterase Type 5 Inhibitor in Humans"],"prefix":"10.1002","volume":"40","author":[{"given":"Mengting","family":"Jia","sequence":"first","affiliation":[{"name":"Tianjin University of Traditional Chinese Medicine  Tianjin China"},{"name":"Shanghai Center for Drug Metabolism and Pharmacokinetics Shanghai Institute of Materia Medica, Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin University  Tianjin China"},{"name":"Henan Topfond Pharma Co., Ltd  Zhumadian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Yan","sequence":"additional","affiliation":[{"name":"Shanghai Center for Drug Metabolism and Pharmacokinetics Shanghai Institute of Materia Medica, Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haonan","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin University of Traditional Chinese Medicine  Tianjin China"},{"name":"Shanghai Center for Drug Metabolism and Pharmacokinetics Shanghai Institute of Materia Medica, Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junchen","family":"Wang","sequence":"additional","affiliation":[{"name":"Henan Topfond Pharma Co., Ltd  Zhumadian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy the Second Affiliated Hospital of Soochow University  Suzhou Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Center for Drug Metabolism and Pharmacokinetics Shanghai Institute of Materia Medica, Chinese Academy of Sciences  Shanghai China"},{"name":"Shenyang Pharmaceutical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7672-9952","authenticated-orcid":false,"given":"Xingxing","family":"Diao","sequence":"additional","affiliation":[{"name":"Tianjin University of Traditional Chinese Medicine  Tianjin China"},{"name":"Shanghai Center for Drug Metabolism and Pharmacokinetics Shanghai Institute of Materia Medica, Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30197"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.podrm.2023.11.006"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2016.08.001"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijir.3901208"},{"issue":"7","key":"e_1_2_9_6_1","first-page":"S9","article-title":"Oral Pharmacotherapy and the Contemporary Evaluation and Management of Erectile Dysfunction","volume":"5","author":"Broderick G. A.","year":"2003","journal-title":"Revista de Urolog\u00eda"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2013.799665"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41443\u2010025\u201001199\u2010z"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2022.2030504"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612003399941"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/3.5.455"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0094\u20100143(21)00697\u20102"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2013.08.023"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2015.118"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2030"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270005276847"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2147\/ciia.2006.1.4.403"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.261"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010022\u201000922\u20106"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/js970486q"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pop.2019.02.006"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx2005212"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2024.2388569"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0008\u20106363(00)00009\u20102"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.14.286"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/bf02889601"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.70289"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2017.12.057"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.13430"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2021.114225"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0302\u20102838(03)00307\u20105"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.06\u20105251.2001.00028.x"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743\u20106109.2004.04021.x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11886\u2010017\u20100889\u2010z"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx300050f"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010021\u201001116\u20104"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602530600952172"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.117.079848"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010020\u20100447\u2010x"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743\u20106109.2012.02822.x"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsm.12285"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29122840"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijir.2010.4"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.1610"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkae240"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2015.09.001"}],"container-title":["Biomedical Chromatography"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.70495","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bmc.70495","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.70495","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T06:21:17Z","timestamp":1781763677000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bmc.70495"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,26]]},"references-count":45,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/bmc.70495"],"URL":"https:\/\/doi.org\/10.1002\/bmc.70495","archive":["Portico"],"relation":{},"ISSN":["0269-3879","1099-0801"],"issn-type":[{"value":"0269-3879","type":"print"},{"value":"1099-0801","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,26]]},"assertion":[{"value":"2026-03-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70495"}}