Background
Premature ejaculation (PE) is the most common type of male sexual disorder with important psychological consequences. Dapoxetine (DPX), a recently approved drug for the treatment of PE, suffers from low bioavailability with large variability that ranges from 15-76% (mean 42%) after oral administration. The
Conclusion
The clinical findings suggest 194% enhancement of relative bioavailability of the optimized DPX-loaded NPs, potentially leading to a decrease in therapeutic dose and associated side effects in the treatment of PE.
Methods
We investigated the effect of ALA concentration, PVA concentration and stirring rate on nanoparticle size (Y1), zeta potential (Y2), initial DPX release (Y3) and cumulative DPX release (Y4). In addition, in vivo pharmacokinetic study was performed for the optimized DPX formulation on human healthy volunteers compared with marketed DPX tablet.
Results
The optimized DPX-loaded NPs showed Y1, Y2, Y3, and Y4 of 159.24 nm, 19.14 mV, 25.31% and 95.9 %, respectively. A single oral dose of 30 mg of optimized DPX-loaded NPs to human volunteers resulted in 2-fold improvement of AUC (1376.145±339.592 vs 709.178±146.307 in DPX), 4-fold increase in tmax (2.5±0.314 vs 0.583±0.144), prolongation of MRT (7.637±1.373 compared to 6.031±1.826 h), but with reduction in t1/2 (5.283±1.077 vs 8.452±2.813).