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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. [ABSTRACT FROM AUTHOR]

Immunotherapy has led to an expansion of the treatment of malignancies, but its effect in prostate cancer (PCa) patients is modest. Chemoimmunotherapy is a promising approach that has attracted substantial attention. Although the widely used clinical chemotherapeutic drug doxorubicin (DOX) elicits immunogenic cell death (ICD), its weak ICD effect and the abnormal vasculature of tumors severely limit its efficacy in chemoimmunotherapy. Ingenol-3-angelate (I3A), an emerging antitumor drug with dual chemotherapeutic and immune response-eliciting effects, is expected to exert synergistic effects when administered in combination with DOX. I3A induces the ICD of PCa cells by triggering mitophagy and apoptosis and promotes the normalization of tumor vessels, resulting in sufficient infiltration of immune cells into tumors. A synergistic effect of I3A and DOX was observed in vitro at a molar ratio of 1:4. To codeliver this ratio of I3A and DOX to tumor and ensure their uptake, we designed a dual-targeting delivery system, polylactide-poly(ethylene) glycol-2-(3-((S)-5-amino-1-carboxypentyl)-ureido) pentanedioate/triphenylphosphonium (PLA-PEG-ACUPA/TPP), which targets prostate-specific membrane antigen (PSMA) and mitochondria. Delivery of these nanomedicines led to inhibited tumor growth and a strong antitumor immune response. This study sheds light on the mitophagic and antiangiogenic mechanisms underlying I3A treatment of PCa and provides a strategy for combining vascular normalization and chemoimmunotherapy for PCa treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)