{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:53:51Z","timestamp":1787871231887,"version":"build-2784847793"},"reference-count":19,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2006,11,1]],"date-time":"2006-11-01T00:00:00Z","timestamp":1162339200000},"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":[[2006,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Because the treatment of inhalational anthrax cannot be studied in human clinical trials, it is necessary to conduct efficacy studies using a rhesus monkey model. However, the half-life of levofloxacin was approximately three times shorter in rhesus monkeys than in humans. Computer simulations to match plasma concentration profile, area under the concentration-time curve (AUC), and time above MIC for a human oral dose of 500 mg levofloxacin once a day identified a dosing regimen in rhesus monkeys that would most closely match human exposure: 15 mg\/kg followed by 4 mg\/kg administered 12 h later. Approximately 24 h following inhalational exposure to approximately 49 times the 50% lethal doses of\n            <jats:italic>Bacillus anthracis<\/jats:italic>\n            (Ames strain), monkeys were treated daily with vehicle, levofloxacin, or ciprofloxacin for 30 days. Ciprofloxacin was administered at 16 mg\/kg twice a day. Following the 30-day treatment, monkeys were observed for 70 days. Nine of 10 control monkeys died within 9 days of exposure. No clinical signs were observed in fluoroquinolone-treated monkeys during the 30 treatment days. One monkey died 8 days after levofloxacin treatment, and two monkeys from the ciprofloxacin group died 27 and 36 days posttreatment, respectively. These deaths were probably related to the germination of residual spores.\n            <jats:italic>B. anthracis<\/jats:italic>\n            was positively cultured from several tissues from the three fluoroquinolone-treated monkeys that died. MICs of levofloxacin and ciprofloxacin from these cultures were comparable to those from the inoculating strain. These data demonstrate that a humanized dosing regimen of levofloxacin was effective in preventing morbidity and mortality from inhalational anthrax in rhesus monkeys and did not select for resistance.\n          <\/jats:p>","DOI":"10.1128\/aac.00090-06","type":"journal-article","created":{"date-parts":[[2006,10,25]],"date-time":"2006-10-25T20:58:50Z","timestamp":1161809930000},"page":"3535-3542","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Pharmacokinetic Considerations and Efficacy of Levofloxacin in an Inhalational Anthrax (Postexposure) Rhesus Monkey Model"],"prefix":"10.1128","volume":"50","author":[{"given":"L.\u2009Mark","family":"Kao","sequence":"first","affiliation":[{"name":"Johnson &amp; Johnson Pharmaceutical Research and Development, LLC, Raritan, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Bush","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson Pharmaceutical Research and Development, LLC, Raritan, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy","family":"Barnewall","sequence":"additional","affiliation":[{"name":"Battelle Memorial Institute, West Jefferson, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Estep","sequence":"additional","affiliation":[{"name":"Battelle Memorial Institute, West Jefferson, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic W.","family":"Thalacker","sequence":"additional","affiliation":[{"name":"Covance Laboratories Inc., 3301 Kinsman Boulevard, Madison, Wisconsin 53704"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela\u2009H.","family":"Olson","sequence":"additional","affiliation":[{"name":"Battelle Memorial Institute, West Jefferson, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George L.","family":"Drusano","sequence":"additional","affiliation":[{"name":"Ordway Research Institute, Albany, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Minton","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson Pharmaceutical Research and Development, LLC, Raritan, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuchean","family":"Chien","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson Pharmaceutical Research and Development, LLC, Raritan, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Hemeryck","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson Pharmaceutical Research and Development, LLC, Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Kelley","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson Pharmaceutical Research and Development, LLC, Spring House, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200140030-00003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.7.2307-2309.2002"},{"key":"e_1_3_2_4_2","unstructured":"Center for Drug Evaluation and Research. 2002. Draft guidance for industry inhalational anthrax (post-exposure)\u2014developing antimicrobial drugs. Center for Drug Evaluation and Research U.S. Food and Drug Administration Washington D.C."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.10.2256"},{"key":"e_1_3_2_6_2","unstructured":"Clinical and Laboratory Standards Institute. 2005. Performance standards for antimicrobial testing. Ninth M100-S15. Clinical and Laboratory Standards Institute Wayne Pa."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.12.5099-5106.2005"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199732020-00002"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1586\/14787210.1.3.371","volume":"1","year":"2003","unstructured":"Fish, D. N. 2003. Levofloxacin: update and perspectives on one of the original \u2018respiratory quinolones.\u2019 Exp. Rev. Antiinfect. Ther.1:371-387.","journal-title":"Exp. 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Konzig-Schippers, F. Sorgel, and D. U. Holzgrabe. 1998. Plasma protein binding of gyrase inhibitors. J. Pharm. Sci.87:215-220.","journal-title":"J. Pharm. 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