{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:53:07Z","timestamp":1768974787366,"version":"3.49.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"MCTI | Conselho Nacional de Desenvolvimento Cientifico e Tecnologico","award":["144816\/2010-5"],"award-info":[{"award-number":["144816\/2010-5"]}]},{"DOI":"10.13039\/501100004263","name":"Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul","doi-asserted-by":"crossref","award":["11\/0908-5"],"award-info":[{"award-number":["11\/0908-5"]}],"id":[{"id":"10.13039\/501100004263","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Levofloxacin (LEV) is a broad-spectrum fluoroquinolone used to treat pneumonia, urinary tract infections, chronic bacterial bronchitis, and prostatitis. Efflux transporters, primarily P-glycoprotein (P-gp), are involved in LEV's tissue penetration. In the present work, LEV free lung and prostate interstitial space fluid (ISF) concentrations were evaluated by microdialysis in Wistar rats after intravenous (i.v.) and intratracheal (i.t.) administration (7 mg\/kg of body weight) with and without coadministration of the P-gp inhibitor tariquidar (TAR; 15 mg\/kg administered i.v.). Plasma and tissue concentration\/time profiles were evaluated by noncompartmental analysis (NCA) and population pharmacokinetics (popPK) analysis. The NCA showed significant differences in bioavailability (\n            <jats:italic>F<\/jats:italic>\n            ) for the control group (0.4) and the TAR group (0.86) after i.t. administration. A four-compartment model simultaneously characterized total plasma and free lung (compartment 2) and prostate (compartment 3) ISF concentrations. Statistically significant differences in lung and prostate average ISF concentrations and levels of kidney active secretion in the TAR group from those measured for the control group (LEV alone) were observed. The estimated population means were as follows: volume of the central compartment (\n            <jats:italic>V<\/jats:italic>\n            <jats:sub>1<\/jats:sub>\n            ), 0.321 liters; total plasma clearance (CL), 0.220 liters\/h; TAR plasma clearance (CL\n            <jats:sub>TAR<\/jats:sub>\n            ), 0.180 liters\/h. The intercompartmental distribution rate constants (\n            <jats:italic>K<\/jats:italic>\n            values) were as follows:\n            <jats:italic>K<\/jats:italic>\n            <jats:sub>12<\/jats:sub>\n            , 8.826 h\n            <jats:sup>\u22121<\/jats:sup>\n            ;\n            <jats:italic>K<\/jats:italic>\n            <jats:sub>21<\/jats:sub>\n            , 7.271 h\n            <jats:sup>\u22121<\/jats:sup>\n            ;\n            <jats:italic>K<\/jats:italic>\n            <jats:sub>13<\/jats:sub>\n            , 0.047 h\n            <jats:sup>\u22121<\/jats:sup>\n            ;\n            <jats:italic>K<\/jats:italic>\n            <jats:sub>31<\/jats:sub>\n            , 7.738 h\n            <jats:sup>\u22121<\/jats:sup>\n            ;\n            <jats:italic>K<\/jats:italic>\n            <jats:sub>14<\/jats:sub>\n            , 0.908 h\n            <jats:sup>\u22121<\/jats:sup>\n            ;\n            <jats:italic>K<\/jats:italic>\n            <jats:sub>41<\/jats:sub>\n            , 0.409 h\n            <jats:sup>\u22121<\/jats:sup>\n            ;\n            <jats:italic>K<\/jats:italic>\n            <jats:sub>21<\/jats:sub>\n            lung TAR (\n            <jats:italic>K<\/jats:italic>\n            <jats:sub>21LTAR<\/jats:sub>\n            ), 8.883 h\n            <jats:sup>\u22121<\/jats:sup>\n            ;\n            <jats:italic>K<\/jats:italic>\n            <jats:sub>31<\/jats:sub>\n            prostate TAR (\n            <jats:italic>K<\/jats:italic>\n            <jats:sub>31PTAR<\/jats:sub>\n            ), 4.377 h\n            <jats:sup>\u22121<\/jats:sup>\n            . The presence of P-gp considerably impacted the active renal secretion of LEV but had only a minor impact on the efflux from the lung following intratracheal dosing. Our results strongly support the idea of a role of efflux transporters other than P-gp contributing to LEV's tissue penetration into the prostrate.\n          <\/jats:p>","DOI":"10.1128\/aac.02317-15","type":"journal-article","created":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T03:39:48Z","timestamp":1448941188000},"page":"946-954","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration"],"prefix":"10.1128","volume":"60","author":[{"given":"Estevan Sonego","family":"Zimmermann","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande do Sul, Porto Alegre, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Victor","family":"Laureano","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande do Sul, Porto Alegre, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila Neris","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande do Sul, Porto Alegre, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics &amp; Systems Pharmacology, College of Pharmacy, University of Florida at Lake Nona, Orlando, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chakradhar V.","family":"Lagishetty","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics &amp; Systems Pharmacology, College of Pharmacy, University of Florida at Lake Nona, Orlando, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Whocely Victor","family":"de Castro","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Federal University of S\u00e3o Jo\u00e3o del-Rei, Divin\u00f3polis, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Dalla Costa","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande do Sul, Porto Alegre, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Antimicrobial resistance","author":"World Health Organization (WHO)","year":"2014","unstructured":"World Health Organization (WHO). 2014. 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