{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T02:31:11Z","timestamp":1784341871072,"version":"3.55.0"},"reference-count":17,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2010,5,1]],"date-time":"2010-05-01T00:00:00Z","timestamp":1272672000000},"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":[[2010,5]]},"abstract":"ABSTRACT<\/jats:title>\n \n There are few options for prophylaxis after exposure to\n Bacillus anthracis<\/jats:italic>\n , especially in children and women of childbearing potential. Faropenem is a \u03b2-lactam in the penem subclass that is being developed as an oral prodrug, faropenem medoxomil, for the treatment of respiratory tract infections. Faropenem was shown to have\n in vitro<\/jats:italic>\n activity against\n B. anthracis<\/jats:italic>\n strains that variably express the\n bla1<\/jats:italic>\n \u03b2-lactamase (MIC range, \u22640.06 to 1 \u03bcg\/ml). In this study we evaluated the pharmacokinetic-pharmacodynamic (PK-PD) relationships between the plasma faropenem free-drug (\n f<\/jats:italic>\n ) concentrations and efficacy against\n B. anthracis<\/jats:italic>\n in a murine postexposure prophylaxis inhalation model. The plasma PKs and PKs-PDs of faropenem were evaluated in BALB\/c mice following the intraperitoneal (i.p.) administration of doses ranging from 2.5 to 160 mg\/kg of body weight. For the evaluation of efficacy, mice received by inhalation aerosol doses of\n B. anthracis<\/jats:italic>\n (Ames strain; faropenem MIC, 0.06 \u03bcg\/ml) at 100 times the 50% lethal dose. The faropenem dosing regimens (10, 20, 40, and 80 mg\/kg\/day) were administered i.p. at 24 h postchallenge at 4-, 6-, and 12-h intervals for 14 days. The sigmoid maximum-threshold-of-efficacy (\n E<\/jats:italic>\n max<\/jats:sub>\n ) model fit the survival data, in which the free-drug area under the concentration-time curve (\n f<\/jats:italic>\n AUC)\/MIC ratio, the maximum concentration of free drug in plasma (\n fC<\/jats:italic>\n max<\/jats:sub>\n )\/MIC ratio, and the cumulative percentage of a 24-h period that the free-drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (\n f<\/jats:italic>\n %\n T<\/jats:italic>\n MIC<\/jats:sub>\n ) were each evaluated. Assessment of\n f<\/jats:italic>\n %\n T<\/jats:italic>\n MIC<\/jats:sub>\n demonstrated the strongest correlation with survival (\n R<\/jats:italic>\n 2<\/jats:sup>\n = 0.967) compared to the correlations achieved by assessment of\n f<\/jats:italic>\n AUC\/MIC or\n fC<\/jats:italic>\n max<\/jats:sub>\n \/MIC, for which minimal correlations were observed. The 50% effective dose (ED\n 50<\/jats:sub>\n ), ED\n 90<\/jats:sub>\n , and ED\n 99<\/jats:sub>\n corresponded to\n f<\/jats:italic>\n %\n T<\/jats:italic>\n MIC<\/jats:sub>\n values of 10.6, 13.4, and 16.4%, respectively, and\n E<\/jats:italic>\n max<\/jats:sub>\n was 89.3%. Overall, faropenem demonstrated a high level of activity against\n B. anthracis<\/jats:italic>\n in the murine postexposure prophylaxis inhalation model.\n <\/jats:p>","DOI":"10.1128\/aac.00737-08","type":"journal-article","created":{"date-parts":[[2010,2,10]],"date-time":"2010-02-10T04:54:38Z","timestamp":1265777678000},"page":"1678-1683","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Pharmacokinetic-Pharmacodynamic Assessment of Faropenem in a Lethal Murine\n Bacillus anthracis<\/i>\n Inhalation Postexposure Prophylaxis Model"],"prefix":"10.1128","volume":"54","author":[{"given":"Stanley C.","family":"Gill","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Replidyne, Inc., Louisville, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Rubino","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Ordway Research Institute, Albany, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Bassett","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda","family":"Miller","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Ambrose","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Ordway Research Institute, Albany, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujata M.","family":"Bhavnani","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Ordway Research Institute, Albany, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Beaudry","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Replidyne, Inc., Louisville, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Replidyne, Inc., Louisville, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly Clawson","family":"Stone","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Replidyne, Inc., Louisville, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Critchley","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Replidyne, Inc., Louisville, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nebojsa","family":"Janjic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Replidyne, Inc., Louisville, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry S.","family":"Heine","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00251-07"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.11.158"},{"key":"e_1_3_2_4_2","unstructured":"Antimicrob. 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