Search Results (8)

Zika virus (ZIKV) belongs to the Flavivirus genus of the Flaviviridae family, and is a pathogen posing a significant threat to human health. Currently, there is a lack of internationally approved antiviral drugs for the treatment of ZIKV infection, and symptomatic management remains the primary clinical approach. Consequently, the exploration of safe and effective anti-ZIKV drugs has emerged as a paramount imperative in ZIKV control efforts. In this study, we performed a screening of a compound library consisting of 1789 FDA-approved drugs to identify potential agents with anti-ZIKV activity. We have identified dapoxetine, an orally administered selective serotonin reuptake inhibitor (SSRI) commonly employed for the clinical management of premature ejaculation (PE), as a potential inhibitor of ZIKV RNA-dependent RNA polymerase (RdRp). Consequently, we conducted surface plasmon resonance (SPR) analysis to validate the specific binding of dapoxetine to ZIKV RdRp, and further evaluated its inhibitory effect on ZIKV RdRp synthesis using the ZIKV Gluc reporter gene assay. Furthermore, we substantiated the efficacy of dapoxetine in suppressing intracellular replication of ZIKV, thereby demonstrating a concentration-dependent antiviral effect (EC₅₀ values ranging from 4.20 μM to 12.6 μM) and negligible cytotoxicity (CC₅₀ > 50 μM) across diverse cell lines. Moreover, cell fluorescence staining and Western blotting assays revealed that dapoxetine effectively reduced the expression of ZIKV proteins. Collectively, our findings suggest that dapoxetine exhibits anti-ZIKV effects by inhibiting ZIKV RdRp activity, positioning it as a potential candidate for clinical therapeutic intervention against ZIKV infection. Full article

A fast melt tablet (FMT) is well regarded as an alternative delivery system that might help resolve a patient’s non-compliance issue. The main objective of this study was to develop a cocoa butter-based FMT. Additives, namely 5–15% of PEG 6000, beeswax, paraffin wax, and corn starch, were incorporated into the cocoa butter-based FMT to study the effects of these additives with the physical characteristic of a cocoa butter FMT. An optimum-based formulation was chosen according to the desired hardness and disintegration time and the taste masking property achieved with the model drug—dapoxetine. The analysis demonstrated that incorporating beeswax (15%) and paraffin wax (15%) could prolong the disintegration time by at least two-fold. On the contrary, the presence of corn starch was found to cause an increase in the hardness and reduction of the disintegration time. The disintegration mechanism might be presumed due to the synergistic effect of starch swelling and cocoa butter melting. The hardness value and in vitro disintegration time of the optimum formulation were recorded at 2.93 ± 0.22 kg and 151.67 ± 6.98 s. In terms of dissolution, 80% of dapoxetine was released within 30 min and the dissolution profile was comparable to the innovator product. The formulation was palatable and stable for at least 1 year. The exposure of the FMT formulation at 30 °C for 12 months was reported to be stable. Along with the sound palatability profile and high drug load capacity, the current formulation possesses the desired characteristics to be scaled up and marketed. Full article

Dapoxetine is used for the treatment of premature ejaculation. The present study developed an HPLC–MS/MS method to determine the levels of dapoxetine in human plasma processed using simple protein precipitation. Dapoxetine-d₇ was selected as the internal standard. The established method was performed using a mass spectrometer equipped with an electrospray ionization source in multiple positive ion reactions to monitor the mode using the precursor-to-product ion transitions of m/z 306.2–157.2 and m/z 313.2–164.2 for dapoxetine-d7 and dapoxetine, respectively. The method was evaluated based on its selectivity, linearity, limit of quantification, precision, accuracy, matrix effects, dilution integrity, stability, and extraction recovery. As a result of the model used in the present study, the validated linear ranges of dapoxetine were determined to be 2.00~1000 ng/mL in plasma, and the selectivity, precision, accuracy, dilution integrity, stability, and extraction recovery met the accepted standard. No matrix interference was observed. The method was successfully validated and applied to pharmacokinetic studies in healthy Chinese volunteers during the fasting and postprandial periods, respectively. Full article

Restriction measures enacted during the COVID-19 pandemic had severe effects on male sexual and reproductive health. We aimed to investigate the real-life impact and perception of sexual function in 2020 in Italy, as the first Western country experiencing a national lockdown by measuring relative search volume for keywords pertaining to sexual health and behaviors provided by Google Trends and sales data for pro-erectile treatments. No significant change was observed for erectile dysfunction and premature ejaculation. Interest towards most phosphodiesterase type 5 inhibitors decreased significantly during lockdown (e.g., sildenafil, p = 0.0002; tadalafil p = 0.0016), then reverted to pre-lockdown levels (e.g., sildenafil, p < 0.0001; tadalafil p < 0.0001), mirroring a concomitant sales decrement (p = 0.0292). A subsequent recovery to previous levels at the end of the social confinement was also found (e.g., after vs. before lockdown, sildenafil, p = 0.8459; tadalafil p = 0.1166). During lockdown, interest towards pornography significantly increased during restrictions (p = 0.0053) and remained high (after vs. before lockdown, p = 0.0004), whereas interest towards paid and casual sex declined (p = 0.0015 and p = 0.049, respectively), then reverted to previous levels (after vs. before lockdown, p = 0.3969 and 0.8373, respectively). During the first Italian lockdown, we observed a transient but measurable decrease of sexual health-seeking behaviors and changes in sexual behaviors, with unknown impact for sexual medicine and public health. Full article

Determination of the metabolism pathway of xenobiotics undergoing the hepatic pass is a crucial aspect in drug development since the presence of toxic biotransformation products may result in significant side effects during the therapy. In this study, the complete hepatic metabolism pathway of dapoxetine established according to the human liver microsome assay with the use of a high-resolution LC–MS system was described. Eleven biotransformation products of dapoxetine, including eight metabolites not reported in the literature so far, were detected and identified. N-dealkylation, hydroxylation, N-oxidation and dearylation were found to be the main metabolic reactions for the investigated xenobiotic. In silico analysis of toxicity revealed that the reaction of didesmethylation may contribute to the increased carcinogenic potential of dapoxetine metabolites. On the other hand, N-oxidation and aromatic hydroxylation biotransformation reactions possibly lead to the formation of mutagenic compounds. Full article

Topical anesthetics are one of the first line therapeutical options for men with premature ejaculation (PE). Real-life PE management often involves a range of interventions including systemic drug treatments (such as off-label and on-label selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, phosphodiesterase-5 inhibitors (PDE5Is)), topical anesthetic creams and sprays, and behavioral approaches. Among them, on-demand dapoxetine and lidocaine/prilocaine spray formulations are the only approved treatment options for lifelong PE. The earliest strategy to treat PE was based on the use of topical anesthetic agents. The rationale behind the use of anesthetics is that by reducing the glans penis sensitivity, the spinal and cerebral input of sexual arousal impulses may also be reduced. Oral SSRI proved to be effective to treat PE, but their high rate of side effects limit treatment adherence and both short and long term follow up data are lacking. Conversely, topical anesthetics have proved to increase ejaculatory latency, control, and sexual satisfaction in couple affected by PE with limited rates of adverse events. In this context, we aimed to perform a narrative review to summarize the most recent findings regarding the use of topical treatments for PE. Full article

The study aimed at developing a liquisolid tablet (LST) containing tadalafil (TDL) and dapoxetine (DPX) with improved bioavailability as a potential therapy for male sexual dysfunction. A mixture of nonvolatile solvents, namely PEG 200 and Labrasol®, was utilized to prepare LSTs that were assessed for their quality characteristics. The Box–Behnken design (BBD) was employed to statistically explore the effect of the formulation factors on the quality attributes of LSTs. Furthermore, an in vivo pharmacokinetic study was carried out for the optimized LST in comparison with the marketed tablets on healthy human volunteers. The optimized LST revealed acceptable quality limits with enhanced dissolution for both APIs. The pharmacokinetic parameters after oral administration of the optimized LST indicated that the Cmax of TDL in LSTs was 122.61 ng/mL within 2h compared to the marketed tablets, which reached 91.72 ng/mL after 3 h, indicating the faster onset of action. The AUC was improved for TDL in LST (4484.953 vs. 2994.611 ng/mL∙h in the marketed tablet) and DPX in LST (919.633 vs. 794.699 ng/mL∙h in the marketed tablet). This enhancement in bioavailability potentially minimizes the associated side effects and improves the treatment of male sexual dysfunction, particularly for diabetic patients. Full article

Premature ejaculation (PE) is a highly prevalent male sexual dysfunction that is often neglected, presenting a currently unmet therapeutic need. The classification of PE has historically been varied and at times ambiguous, contributing to inaccurate prevalence estimates. This review uses the International Society for Sexual Medicine (ISSM) definition of PE, which includes reduced ejaculatory latency, lack of control and associated negative personal consequences. Patient assessment and management options differ depending on the classification of PE and it is the role of the clinician to appropriately classify patients and be aware of the correct management strategies. This review provides an overall background of PE in terms of classification and underlying physiology, patient assessment and management strategies along with the scientific rationale for treatment. Patients with lifelong and acquired PE are most likely to benefit from combination therapy of pharmacological treatment in the form of selective serotonin re-uptake inhibitor dapoxetine, psychosexual behavioural therapy and psychological therapy. Full article