{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T01:48:35Z","timestamp":1785376115693,"version":"3.55.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T00:00:00Z","timestamp":1391212800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Levofloxacin is a broad-spectrum fluoroquinolone used in the treatment of both acute and chronic bacterial prostatitis. Currently, the treatment of bacterial prostatitis is still difficult, especially due to the poor distribution of many antimicrobials into the prostate, thus preventing the drug to reach effective interstitial concentrations at the infection site. Newer fluoroquinolones show a greater penetration into the prostate. In the present study, we compared the unbound levofloxacin prostate concentrations measured by microdialysis to those in plasma after a 7-mg\/kg intravenous bolus dose to Wistar rats. Plasma and dialysate samples were analyzed using a validated high-pressure liquid chromatography-fluorescence method. Both noncompartmental analysis (NCA) and population-based compartmental modeling (NONMEM 6) were performed. Unbound prostate tissue concentrations represented 78% of unbound plasma levels over a period of 12 h by comparing the extent of exposure (unbound AUC\n            <jats:sub>0\u2013\u221e<\/jats:sub>\n            ) of 6.4 and 4.8 h\u00b7\u03bcg\/ml in plasma and tissue, respectively. A three-compartment model with simultaneous passive diffusion and saturable distribution kinetics from the prostate to the central compartment gave the best results in terms of curve fitting, precision of parameter estimates, and model stability. The following parameter values were estimated by the population model:\n            <jats:italic>V<\/jats:italic>\n            <jats:sub>1<\/jats:sub>\n            (0.38 liter; where\n            <jats:italic>V<\/jats:italic>\n            <jats:sub>1<\/jats:sub>\n            represents the volume of the central compartment), CL (0.22 liter\/h),\n            <jats:italic>k<\/jats:italic>\n            <jats:sub>12<\/jats:sub>\n            (2.27 h\n            <jats:sup>\u22121<\/jats:sup>\n            ),\n            <jats:italic>k<\/jats:italic>\n            <jats:sub>21<\/jats:sub>\n            (1.44 h\n            <jats:sup>\u22121<\/jats:sup>\n            ),\n            <jats:italic>k<\/jats:italic>\n            <jats:sub>13<\/jats:sub>\n            (0.69 h\n            <jats:sup>\u22121<\/jats:sup>\n            ),\n            <jats:italic>V<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            (7.19 \u03bcg\/h),\n            <jats:italic>k<\/jats:italic>\n            <jats:sub>M<\/jats:sub>\n            (0.35 \u03bcg\/ml),\n            <jats:italic>V<\/jats:italic>\n            <jats:sub>3<\/jats:sub>\n            \/fu\n            <jats:sub>prostate<\/jats:sub>\n            (0.05 liter; where fu\n            <jats:sub>prostate<\/jats:sub>\n            represents the fraction unbound in the prostate), and\n            <jats:italic>k<\/jats:italic>\n            <jats:sub>31<\/jats:sub>\n            (3.67 h\n            <jats:sup>\u22121<\/jats:sup>\n            ). The interindividual variability values for\n            <jats:italic>V<\/jats:italic>\n            <jats:sub>1<\/jats:sub>\n            , CL,\n            <jats:italic>V<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            , and\n            <jats:italic>k<\/jats:italic>\n            <jats:sub>M<\/jats:sub>\n            were 21, 37, 42, and 76%, respectively. Our results suggest that levofloxacin is likely to be substrate for efflux transporters in the prostate.\n          <\/jats:p>","DOI":"10.1128\/aac.01884-13","type":"journal-article","created":{"date-parts":[[2013,11,12]],"date-time":"2013-11-12T04:30:35Z","timestamp":1384230635000},"page":"678-686","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Population Pharmacokinetic Modeling of the Unbound Levofloxacin Concentrations in Rat Plasma and Prostate Tissue Measured by Microdialysis"],"prefix":"10.1128","volume":"58","author":[{"given":"Felipe K.","family":"Hurtado","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Derendorf","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guenther","family":"Hochhaus","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Dalla Costa","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-005-0018-9"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/46.2.157"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1439-0272.2003.00568.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2008.07495.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.1.293-297.2001"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2007.08.025"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.8.2046-2051.2000"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200363240-00008"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1159\/000329520"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200932050-00001"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm476"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.10.2345"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002280100301"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012081501464"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.10230"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2011.29"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2008.02.023"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2008.08.020"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01323-12"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(00)00107-1"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2010.05.023"},{"key":"e_1_3_2_23_2","volume-title":"Applied biopharmaceutics and pharmacokinetics","author":"Shargel L","year":"2005","unstructured":"ShargelLWu-PongSYuABC. 2005. 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