{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T14:15:18Z","timestamp":1785334518589,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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\u2013Dawley 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\u2013125.00% 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 \u2265 30 threshold. Results: Imaging confirmed selective distribution within the reproductive tract after vas-deferens delivery. In plasma, VS substantially reduced systemic exposure compared with IV: Cmax was 4.74 \u03bcg\/mL (VS) versus 10.72 \u03bcg\/mL (IV), and AUC0-24 was 15.47 versus 28.59 \u03bcg\u00b7h\/mL. In the prostate, VS maintained comparable or numerically higher exposure: Cmax was 61.96 \u03bcg\/g (VS) versus 52.02 \u03bcg\/g (IV), and AUC0-24 was 235.77 versus 208.77 \u03bcg\u00b7h\/g. The tissue distribution factor fT was substantially elevated in VS (2.26; 95% CI: 1.58\u20133.19) compared with IV (1.06; 95% CI: 0.89\u20131.30). Bioequivalence-style analysis demonstrated that plasma GMRs for AUC0-24 and Cmax fell well below 80%, confirming reduced systemic burden, while prostate GMRs were maintained, and the prostate-to-plasma AUC ratio GMR was increased. Time-dependent partial AUC analyses revealed that VS significantly elevated the prostate-to-plasma exposure ratio. PK\/PD evaluation showed that at 24 h, prostate fAUC\/MIC against Enterobacteriaceae (MIC = 0.5 \u03bcg\/mL) was 37.7 (VS) versus 33.4 (IV), with corresponding PTA values of 97% and 94%, while plasma fAUC\/MIC remained substantially lower in the VS group. Conclusions: Trans-vas-deferens administration of levofloxacin via a novel injection device effectively reduced systemic drug exposure while maintaining or enhancing prostate tissue concentrations, thereby widening the therapeutic window and reducing systemic drug exposure.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080931","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:53:31Z","timestamp":1785333211000},"page":"931","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Prostatic Delivery of Levofloxacin via a Novel Vas-Deferens Injection Device: A Pharmacokinetic Study in Rats"],"prefix":"10.3390","volume":"18","author":[{"given":"Haiming","family":"Cao","sequence":"first","affiliation":[{"name":"The Department of Urology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Wu","sequence":"additional","affiliation":[{"name":"The Department of Urology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingwei","family":"Zhan","sequence":"additional","affiliation":[{"name":"The Department of Urology, Hangzhou TCM Hospital of Zhejiang Chinese Medical University, Hangzhou 310007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Ma","sequence":"additional","affiliation":[{"name":"The School of Pharmacy, Nanjing Technology University, Nanjing 211816, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"The School of Pharmacy, Nanjing Technology University, Nanjing 211816, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Shang","sequence":"additional","affiliation":[{"name":"The Department of Urology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210007, China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1001\/jama.282.3.236","article-title":"NIH Consensus Definition and Classification of Prostatitis","volume":"282","author":"Krieger","year":"1999","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3433","DOI":"10.1007\/s00345-020-03580-7","article-title":"The Use of Lactobacillus Casei DG\u00ae Prevents Symptomatic Episodes and Reduces the Antibiotic Use in Patients Affected by Chronic Bacterial Prostatitis: Results from a Phase IV Study","volume":"39","author":"Cai","year":"2021","journal-title":"World J. 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