{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:25:45Z","timestamp":1787199945716,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    TPN171 is a potent phosphodiesterase type 5 inhibitor used to treat pulmonary arterial hypertension and erectile dysfunction, primarily metabolized by CYP3A4. This study aimed to evaluate its drug\u2013drug interaction (DDI) potential and determine the optimal dosing when co\u2010administered with CYP3A4 modulators. A physiologically based pharmacokinetic (PBPK) model was developed and validated using clinical DDI data for itraconazole (strong CYP3A4 inhibitor) and rifampin (strong CYP3A4 inducer). The model was then applied to predict DDIs with moderate (diltiazem, fluconazole) and mild (fluvoxamine) inhibitors, as well as moderate (efavirenz) and mild (zanubrutinib) inducers. Predicted AUC\n                    <jats:sub>0\u2212t<\/jats:sub>\n                    ratios aligned with observed data: itraconazole (2.42\u2010fold predicted vs. 2.67\u2010 fold observed) and rifampicin (0.14\u2010fold predicted vs. 0.096\u2010fold observed). For other modulators, geometric mean AUC\n                    <jats:sub>0\u2212t<\/jats:sub>\n                    ratios were 2.40 with diltiazem, 3.27 with fluconazole (400\u2009mg), 2.07 with fluconazole (100\u2009mg), 1.16 with fluvoxamine, 0.53 with efavirenz, and 0.70 with zanubrutinib. These simulations indicate that strong and moderate CYP3A4 inhibitors and inducers significantly alter TPN171 exposure, whereas weak modulators have no clinically meaningful impact. These findings provide a scientific basis for dose recommendations when TPN171 is used with CYP3A4 modulators.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70298","type":"journal-article","created":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T03:12:27Z","timestamp":1784430747000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Physiologically Based Pharmacokinetic Model to Predict Potential Drug\u2013Drug Interactions of\n                    <scp>TPN171<\/scp>\n                    , a Novel Phosphodiesterase Type 5 Inhibitor"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7988-5715","authenticated-orcid":false,"given":"Guanghui","family":"Tian","sequence":"first","affiliation":[{"name":"Vigonvita Life Sciences co., Ltd.  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai PharmoGo co., Ltd  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"Vigonvita Life Sciences co., Ltd.  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Vigonvita Life Sciences co., Ltd.  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Vigonvita Life Sciences co., Ltd.  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5170-9152","authenticated-orcid":false,"given":"Jiaxiang","family":"Juan","sequence":"additional","affiliation":[{"name":"Vigonvita Life Sciences co., Ltd.  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanqin","family":"Duan","sequence":"additional","affiliation":[{"name":"Vigonvita Life Sciences co., Ltd.  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2900-6700","authenticated-orcid":false,"given":"Jianghong","family":"Pei","sequence":"additional","affiliation":[{"name":"Vigonvita Life Sciences co., Ltd.  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2492-3219","authenticated-orcid":false,"given":"Jingying","family":"Jia","sequence":"additional","affiliation":[{"name":"Shanghai Xuhui Central Hospital\/Zhongshan\u2010Xuhui Hospital Fudan University  Shanghai China"},{"name":"Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00123"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2013.06.062"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm301159y"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijir.3901207"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.111128"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-013-1048-9"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S308610"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2019.05.001"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-022-00922-6"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jsxmed\/qdaf109"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo13080897"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2025.06.005"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.37"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2014.46"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph20043473"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2017.1323136"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12010045"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-016-1951-z"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00833-6"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12343"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-016-0787-2"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-006-9210-3"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-014-0188-4"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0330-y"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12605"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12070"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-021-04292-4"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13184"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-021-03194-x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1535"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.8b00129"}],"container-title":["CPT: Pharmacometrics &amp; 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