{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T05:01:57Z","timestamp":1789794117280,"version":"4.0.1"},"reference-count":23,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"\n Aim<\/jats:title>\n \n Interindividual variability in sildenafil response among pulmonary hypertension patients (PH) may be influenced by\n CYP3A5<\/jats:italic>\n polymorphisms.\n CYP3A5*3<\/jats:italic>\n allele reduces CYP3A5 activity and affects sildenafil metabolism. This study investigated the associations between\n CYP3A5<\/jats:italic>\n genotype and plasma concentrations of sildenafil and\n N<\/jats:italic>\n \u2010desmethyl sildenafil, as well as clinical outcomes, in PH.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A cross\u2010sectional study of 92 patients with PH was conducted. Blood samples were collected at trough and 1\u00a0h after sildenafil administration (C1h). Plasma concentrations were quantified by HPLC, and\n CYP3A5<\/jats:italic>\n genotypes were determined by real\u2010time PCR with TaqMan probes.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Thirteen (14.13%) patients carried the\n CYP3A5 *1\/*1<\/jats:italic>\n genotype, and 79 (85.87%) carried the\n CYP3A5*3<\/jats:italic>\n allele.\n CYP3A5*3<\/jats:italic>\n allele carriers had a significantly higher mean C1h sildenafil concentration\u2010to\u2010dose (C\/D) ratio than\n CYP3A5*1\/*1<\/jats:italic>\n carriers (3.61\u2009\u00b1\u20092.69\n vs<\/jats:italic>\n . 2.66\u2009\u00b1\u20091.20\u2009ng\/mL\/mg;\n p<\/jats:italic>\n \u2009=\u20090.043). The mean C1h of sildenafil, trough sildenafil concentration and trough sildenafil C\/D ratio were higher in\n CYP3A5*<\/jats:italic>\n 3 carriers, but not statistically significant. The trough and C1h of\n N<\/jats:italic>\n \u2010desmethyl sildenafil and their corresponding C\/D ratios were lower in\n CYP3A5*3<\/jats:italic>\n carriers but did not reach statistical significance.\n CYP3A5*3<\/jats:italic>\n allele carriers showed greater improvement in 6\u2010min walk distance (33.74\u2009\u00b1\u200943.46\u2009m\n vs<\/jats:italic>\n . \u20135.58\u2009\u00b1\u200944.52\u2009m;\n p<\/jats:italic>\n \u2009=\u20090.005), WHO functional class (32.00%\n vs<\/jats:italic>\n . 15.39%;\n p<\/jats:italic>\n \u2009=\u20090.042) and EmPHasis\u201010 scores (\u22124.15\u2009\u00b1\u20096.46\n vs<\/jats:italic>\n . 1.08\u2009\u00b1\u20093.80;\n p<\/jats:italic>\n \u2009=\u20090.009).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The\n CYP3A5*3<\/jats:italic>\n allele is associated with higher sildenafil exposure and superior clinical outcomes. Therefore,\n CYP3A5<\/jats:italic>\n genotyping may facilitate personalized assessment of sildenafil efficacy and clinical outcomes.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/bcp.70826","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:17:13Z","timestamp":1789791433000},"source":"Crossref","is-referenced-by-count":0,"title":["CYP3A5<\/i>\n genetic variability influences sildenafil and metabolite in pulmonary hypertension"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8201-3208","authenticated-orcid":false,"given":"Pranisa","family":"Wongwien","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine Khon Kaen University Khon Kaen Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burabha","family":"Pussadhamma","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Medicine, Faculty of Medicine Khon Kaen University Khon Kaen Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirimas","family":"Kanjanawart","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine Khon Kaen University Khon Kaen Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thikhumporn","family":"Areesinpitak","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine Khon Kaen University Khon Kaen Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1631-3178","authenticated-orcid":false,"given":"Nontaya","family":"Nakkam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine Khon Kaen University Khon Kaen Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chingching","family":"Foocharoen","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Faculty of Medicine Khon Kaen University Khon Kaen Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6722-8796","authenticated-orcid":false,"given":"Wichittra","family":"Tassaneeyakul","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine Khon Kaen University Khon Kaen Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4706-5771","authenticated-orcid":false,"given":"Suda","family":"Vannaprasaht","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine Khon Kaen University Khon Kaen Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac237"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01325\u20102024"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0306\u20105251.2001.00027.x"},{"key":"e_1_2_11_5_1","unstructured":"Pfizer\u2010Laboratories.VIAGRA\u2010sildenafil citrate tablet prescriping information. FDA.1998[cited 2022 Oct 26]. Available from:https:\/\/labeling.pfizer.com\/ShowLabeling.aspx?id=652"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2306\/scienceasia1513\u20101874.2020.050"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201076085\u20103"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0263621"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.690"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pul2.12304"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01323\u20102024"},{"issue":"2","key":"e_1_2_11_12_1","first-page":"1","article-title":"Validation of an HPLC method for determining sildenafil and NDMS plasma concentrations in pulmonary arterial hypertension","volume":"108","author":"Wongwien P","year":"2025","journal-title":"J Med Assoc Thai"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01324\u20102024"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465\u20109921\u201012\u201099"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70234"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2017.8"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e32834b79e6"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2013.804063"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010007\u20100408\u2010z"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12872\u2010017\u20100674\u20103"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050010"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.068107"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890\u2010017\u20100374\u2010x"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2007.11.019"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70826","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bcp.70826","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70826","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:17:14Z","timestamp":1789791434000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":23,"alternative-id":["10.1002\/bcp.70826"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70826","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,18]]},"article-number":"bcp.70826"}}