{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:54:19Z","timestamp":1773017659160,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012899","name":"Lanzhou University","doi-asserted-by":"publisher","award":["20240050036"],"award-info":[{"award-number":["20240050036"]}],"id":[{"id":"10.13039\/100012899","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dapoxetine is a short\u2010acting selective serotonin reuptake inhibitor used to treat premature ejaculation. However, its clinical effectiveness is challenged by substantial inter\u2010individual variability in pharmacokinetics, as both the drug's therapeutic efficacy and the incidence of adverse reactions are highly dependent on its exposure. This study aims to develop a population pharmacokinetic model for dapoxetine, to investigate the sources of the variability, and to identify demographic and pharmacogenetic factors that influence drug exposure. The pharmacokinetic data for this analysis were obtained from a bioequivalence study conducted in 39 healthy Chinese male subjects. As part of this study, all volunteers were genotyped for the CYP3A4*1G, CYP3A5*3, CYP2D6*10, and CYP2D6*41 allelic variants. Population pharmacokinetic modeling was performed in Monolix. The final model was then used to simulate and compare the effect of different covariate levels on dapoxetine exposure. A two\u2010compartment model with first\u2010order absorption and an absorption lag time best described the pharmacokinetics of dapoxetine. The population parameters for apparent clearance (CL\/F), apparent intercompartmental clearance (Q\/F), apparent central volume of distribution (Vc\/F), apparent peripheral volume of distribution (Vp\/F), absorption lag time (Tlag), and absorption rate constant (ka) were 37.8 L\/h, 17.2 L\/h, 65.6 L, 191.7 L, 0.68 h, and 1.29\/h, respectively. CYP2D6*10 and CYP2D6*41 alleles were found to be significant covariates on CL\/F. The CYP3A4*1G allele influenced Q\/F, while body mass index (BMI) was a significant covariate on Vc\/F. Our analysis identified CYP2D6*10 and CYP2D6*41 polymorphisms as the significant factors contributing to inter\u2010individual variability and influencing drug exposure.<\/jats:p>","DOI":"10.1002\/jcph.70117","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T10:05:52Z","timestamp":1759313152000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetics of Dapoxetine in Healthy Chinese Male Subjects"],"prefix":"10.1002","volume":"66","author":[{"given":"Libin","family":"Pu","sequence":"first","affiliation":[{"name":"School of Pharmacy Lanzhou University  Lanzhou Gansu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Lanzhou University  Lanzhou Gansu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuqiang","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Pharmacy Lanzhou University  Lanzhou Gansu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haobo","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Mathematics and Statistics Lanzhou University  Lanzhou Gansu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiming","family":"Wang","sequence":"additional","affiliation":[{"name":"Lianhu District Administration for Market Regulation  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Third People's Hospital of Chengdu  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Qiu","sequence":"additional","affiliation":[{"name":"Phase I Clinical Unit Lanzhou University Second Hospital  Lanzhou Gansu China"},{"name":"Pharmacy Department Lanzhou University Second Hospital  Lanzhou Gansu China"},{"name":"Cuiying Biomedical Research Center The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou Gansu China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"issue":"10","key":"e_1_2_11_2_1","first-page":"737","article-title":"Premature ejaculation: a clinical review for the general physician","volume":"44","author":"Chung E","year":"2015","journal-title":"Aust Fam Physician"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/aja.aja_122_18"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.4137\/CMRH.S7337"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1677\u20105538.IBJU.2023.9908"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585\u2010022\u201000639\u20105"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2009.01.025"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1071\/SH18005"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.5144\/0256\u20104947.2018.366"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270006291033"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1393"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008324695"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325\u2010019\u201000982\u2010x"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2391"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S97789"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12612"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009359183"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.866"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11111295"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010017\u20100832\u2010z"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2019.04.013"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.919"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.2165\/11318100\u2010000000000\u201000000"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.18636"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70117","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70117","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:54:18Z","timestamp":1773014058000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":23,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/jcph.70117"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70117","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]},"assertion":[{"value":"2025-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70117"}}