{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:34:18Z","timestamp":1792067658170,"version":"4.4.0"},"reference-count":63,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"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>Background\/Objectives: Levofloxacin (LVX) is a fluoroquinolone approved for the treatment of bacterial pneumonia, sinusitis, and prostatitis. Emerging in vitro and preclinical evidence suggests that efflux transporters are involved in LVX\u2019s target tissue site distribution. Methods: The objective of this research was to characterize tissue exposure using a physiologically based pharmacokinetic (PBPK) model to be able to make more educated choices for optimal doses using target site pharmacokinetics data. Results: The final PBPK model in humans was applied to simulate free target site concentrations of LVX in lung and prostate, linking to minimum inhibitory concentrations (MIC) to assess appropriateness of currently approved dosing regimens for infections in both tissues. The clinical PBPK model was able to reproduce total plasma as well as free lung and prostate exposure of LVX in humans. Efflux transporters participate in LVX distribution to prostatic but not pulmonary tissue. Our results show a good penetration of LVX in both tissues with unbound partition coefficient (Kp,uu) equal to 0.79 and 0.72 for lung and prostate, respectively. Since LVX penetration in lung and prostate is similar, different sensitivities of the pathogens to LVX will dictate the effectiveness of the approved therapeutic regimen in the treatment of bacterial pneumonia, sinusitis, and prostatitis. Conclusions: Our research provides relevant insight into LVX\u2019s target site exposure in lung and prostate. When integrated with pathogen-specific susceptibility data, these findings can be applied to refine current dosing regimens and help optimize the pharmacological treatment outcomes.<\/jats:p>","DOI":"10.3390\/pharmaceutics18010107","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T18:40:09Z","timestamp":1768329609000},"page":"107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Translational Model to Predict Lung and Prostate Distribution of Levofloxacin in Humans"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1561-2750","authenticated-orcid":false,"given":"Estevan","family":"Sonego Zimmermann","sequence":"first","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9227-2991","authenticated-orcid":false,"given":"Teresa","family":"Dalla Costa","sequence":"additional","affiliation":[{"name":"Pharmacokinetics and PK\/PD Modeling Laboratory, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre 90610000, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7932-8599","authenticated-orcid":false,"given":"Brian","family":"Cicali","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Almoslem","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA"},{"name":"Certara, Certara Drug Development Solutions, Randor, PA 19087, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Cristofoletti","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4998-1167","authenticated-orcid":false,"given":"Stephan","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1473-3099(17)30753-3","article-title":"WHO Pathogens Priority List Working Group. 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