Population Pharmacokinetics of Dapoxetine in Healthy Chinese Male Subjects.
Dapoxetine is a short‐acting selective serotonin reuptake inhibitor used to treat premature ejaculation. However, its clinical effectiveness is challenged by substantial inter‐individual variability in pharmacokinetics, as both the drug's therapeutic efficacy and the incidence of adverse reactions a...
| Publicado en: | Journal of Clinical Pharmacology Vol. 66; no. 2; pp. 1 - 10 |
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| Autores principales: | , , , , , , |
| Formato: | equations & formulas research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Feb2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=194233214&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 194233214 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00912700 5WH jtl: Journal of Clinical Pharmacology issn: 00912700 maglogo: Y pubinfo: dt: Feb2026 vid: 66 iid: 2 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 194233214 188341753 194233214 194233214 10.1002/jcph.70117 194233214 ppf: 1 ppct: 9 formats: tig: atl: Population Pharmacokinetics of Dapoxetine in Healthy Chinese Male Subjects. aug: au: Pu, Libin Wu, Tong Bai, Fuqiang Lu, Haobo Wang, Yiming Gao, Yuan Qiu, Wen affil: School of Pharmacy, Lanzhou University, Lanzhou Gansu,, China sug: subj: Amines Pharmacokinetics Serotonin Uptake Inhibitors Pharmacokinetics Men's Health Prediction Models Sociodemographic Factors Pharmacogenetics Serotonin Uptake Inhibitors Administration and Dosage Human Male Young Adult Funding Source China Genetic Profile Alleles Simulations Time Academic Medical Centers Polymorphism, Genetic Body Mass Index Serotonin Uptake Inhibitors Blood Preprocedural Fasting Postprandial Period Liquid Chromatography-Mass Spectrometry Descriptive Statistics Data Analysis Software Algorithms Age Factors Body Weight Biological Markers Blood Aspartate Aminotransferase Blood Alanine Aminotransferase Blood Bilirubin Blood Creatinine Blood Blood Urea Nitrogen Evaluation Goodness of Fit Chi Square Test Confidence Intervals Premature Ejaculation Drug Therapy Comparative Studies Cytochrome P-450 Enzyme System Genotype Male ab: Dapoxetine is a short‐acting selective serotonin reuptake inhibitor used to treat premature ejaculation. However, its clinical effectiveness is challenged by substantial inter‐individual 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‐compartment model with first‐order 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‐individual variability and influencing drug exposure. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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