Impacts of Cytochrome P450 2D6*10 Allele and a High-Fat Meal on the Pharmacokinetics of Dapoxetine in Healthy Chinese Men: A Single-Dose, Two-Treatment Study

Dapoxetine is the first oral medication specifically developed for the on‐demand treatment of premature ejaculation. The pharmacokinetics and safety of 30 mg (n = 40) and 60 mg (n = 38) dapoxetine in healthy Chinese under fasted and fed states were assessed in 2 studies. Both studies are random, single‐center, 2‐period, open‐label, 2‐way crossover designs. Plasma concentration of dapoxetine was determined by high‐performance liquid chromatography–tandem mass spectrometry, and the pharmacokinetic parameters were calculated using noncompartmental analysis. Dapoxetine was quickly absorbed and reached maximum concentration 1 to 3 hours after oral administration. Elimination was biphasic, and the plasma concentration decreased to 3% to 7% of maximum concentration by 24 hours while half‐life was 15 to 18 hours. Meantime, high‐fat meals slightly increased its exposure. Both doses of dapoxetine were well tolerated. The adverse events in the high‐dose group under fasted and fed states were 37.9% and 19.0%, respectively.

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 87%

Pharmacokinetics and Safety of Dapoxetine Hydrochloride in Healthy Chinese Men: Impact of Dose and High‐Fat Meal

Liu

Yan

et al. 2021

“…Based on the results of this study, a high‐fat meal impacted the drug concentration‐time curve of dapoxetine and promoted its absorption. The results of this study were consistent with the results of a previous study, which demonstrated that coadministration of dapoxetine and a high‐fat meal resulted in a significant increase (23.6%) in the AUC 0‐48 as well as an approximately 1.1‐hour delay in the T max 20 . However, compared with the previous study, we observed a larger increase in the AUC values under the fed conditions, which could be attributed to the fasting versus fed comparisons being based on different cohorts as opposed to a crossover study or because the number of study samples was too small.…”

Section: Discussionsupporting

confidence: 91%

“…It was observed that some subjects had AEs during each drug administration, although their C max was not very high; few subjects had a high C max , but drug administration was well tolerated, and there were no AEs. Based on Tang's report regarding the relationship between CYP2D6 and the absorption of dapoxetine, it was concluded that individual differences may lead to this phenomenon 20 . The relationship between individual differences and genes regarding the observations in this study needs to be further explored.…”

Section: Discussionmentioning

confidence: 77%

“…High‐fat foods facilitate drug absorption through multiple mechanisms, such as prolonging drug residence time by lowering gastric emptying. Also, the solubility of sparingly soluble drugs can be enhanced by promoting bile secretion 20 . Based on the results of this study, a high‐fat meal impacted the drug concentration‐time curve of dapoxetine and promoted its absorption.…”

Section: Discussionmentioning

confidence: 79%

See 1 more Smart Citation

Bioequivalence Analysis of 2 Dapoxetine Hydrochloride Formulations in Healthy Chinese Male Volunteers Under Fed and Fasting Conditions: A Randomized, Open‐Label, 2‐Sequence, 2‐Period, 2‐Way Crossover Study

Yan

Tan³

et al. 2021

This study assessed whether the reference and test formulations of dapoxetine hydrochloride were bioequivalent under fed and fasting conditions postadministration of a single dose as well as evaluated the safety profile of these 2 formulations. This study was a randomized, single‐center, 2‐period, open‐label, 2‐way crossover design study with a washout period of 7 days between each period. The study included 80 subjects, 40 under fed and 40 under fasting conditions. During each study period, the subjects were administered a single oral dose of either the reference or the test formulation, followed by collection of plasma samples 70 hours postdose. High‐performance liquid chromatography‐tandem mass spectrometry (HPLC‐MS/MS) was performed to determine the concentrations of dapoxetine in plasma samples along with the calculation of Cmax, AUC0‐t, and AUC0‐inf. In addition, adverse events were monitored to determine the safety of these formulations. The geometric mean ratio (90%CI) for the reference and test formulations was 86% to 100%, 89% to 103%, and 89% to 103% under fasting conditions and 92% to 107%, 91% to 100%, and 92% to 101% under fed conditions for Cmax, AUC0‐t, and AUC0‐inf, respectively. The 90%CIs for the test/reference ratio for AUC and Cmax were within the acceptable limits of bioequivalence, thus demonstrating bioequivalence for these 2 dapoxetine hydrochloride formulations.

Bioequivalence Assessment of Two Dapoxetine Hydrochloride Formulations in Healthy Chinese Males Under Fasted and Fed Conditions

Li,

Zhang,

Xie

et al. 2024

This study evaluated the bioequivalence of the newly developed dapoxetine hydrochloride tablet relative to the marketed reference product by comparing their pharmacokinetic profiles under fasted and fed conditions. A total of 60 healthy Chinese male subjects participated in a single‐center, 2‐period, 2‐sequence, randomized, open‐label, self‐crossover study with a washout period of 14 days, 30 in the fasted group and 30 in the fed group. Following a single 30‐mg oral dose of the test or reference dapoxetine formulation, blood samples were collected before dosing to 72 hours after dosing. Liquid chromatography‐tandem mass spectrometry was performed to measure plasma concentration of dapoxetine and determine pharmacokinetic parameters through noncompartmental analysis. The vital signs and adverse events were also monitored during the study. The 90% confidence intervals of the geometric mean ratios for maximum plasma concentration, area under the plasma concentration‐time curve from time 0 to the last concentration time, and area under the plasma concentration‐time curve from time 0 extrapolated to infinity of the 2 dapoxetine formulations completely fell within the regulatory criteria for bioequivalence of 80%‐125%. In addition, both dapoxetine hydrochloride formulations were generally well tolerated. The generic dapoxetine hydrochloride tablet was bioequivalent to the marketed reference product in healthy Chinese men with no discernible safety differences.