Targeted Prostatic Delivery of Levofloxacin via a Novel Vas-Deferens Injection Device: A Pharmacokinetic Study in Rats
Abstract
Objective: Current pharmacological treatments for prostate diseases are limited by poor drug penetration into the prostate and systemic adverse effects. This study evaluated whether a novel vas-deferens injection device could improve targeted delivery of levofloxacin to the prostate. Methods: Healthy adult male Sprague-Dawley rats received a single dose of levofloxacin by either intravenous administration (IV) or trans-vas-deferens administration using a novel disposable device (VS). Plasma and prostate samples were collected from 0.5 to 24 h and analyzed by LC-MS/MS. Iodixanol micro-CT imaging was used to visualize the local delivery pathway. Pharmacokinetic evaluation included observed composite-profile Cmax/Tmax, AUC0-24, and fT. Time-dependent tissue selectivity was evaluated through partial AUC analyses, prostate-to-plasma exposure ratios, and pointwise concentration ratios. A bioequivalence-style framework was applied to compare relative exposure parameters using geometric mean ratios (GMRs) with the 80.00-125.00% reference interval. Exploratory PK/PD evaluation combined literature-derived free-drug fractions (fut_plasma = 0.55, fut_prostate = 0.080) to estimate fAUC/MIC against representative uropathogens, supplemented by Monte Carlo simulation (n = 5000) to estimate probability of target attainment (PTA) at an fAUC/MIC ≥ 30 threshold. Results: Imaging confirmed selective distribution within the reproductive tract after vas-deferens delivery. In plasma, VS…
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