{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:29:05Z","timestamp":1772162945053,"version":"3.50.1"},"reference-count":22,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T00:00:00Z","timestamp":1322697600000},"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":[[2011,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    ACHN-490 is an aminoglycoside with activity against multidrug-resistant pathogens, including those resistant to currently used aminoglycosides. Two randomized, double-blind, placebo-controlled clinical studies investigated the pharmacokinetics (PK), safety, and tolerability of ACHN-490 injection in healthy subjects. Study 1 used a parallel-group design with escalating single (SD) and multiple doses (MD). Study 2 explored a longer duration of the highest dose tolerated in the first study. Subjects were randomly assigned to receive either ACHN-490 injection or a placebo administered by a 10-min intravenous infusion. Study 1 enrolled 39 subjects (30 active and 9 placebo) and consisted of a single dose of 1 mg\/kg body weight followed by ascending SD and MD cohorts of 4, 7, 11, and 15 mg\/kg for 10, 10, 5, and 3 days, respectively. Study 2 enrolled 8 subjects (6 active and 2 placebo) who received 15 mg\/kg for 5 days. Safety was assessed from adverse event (AE) reporting, standard clinical laboratory procedures, and testing for renal, cochlear, and vestibular function. ACHN-490 exhibited linear and dose-proportional PK, with agreement between the studies for PK parameters assessed. The 15-mg\/kg dose did not accumulate with repeated dosing over 5 days. Mean steady-state (\u00b1standard deviation) area under the concentration-time curve from 0 to 24 h (AUC\n                    <jats:sub>0-24<\/jats:sub>\n                    ), maximum concentration of drug in serum (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ), half-life (\n                    <jats:italic>t<\/jats:italic>\n                    <jats:sub>1\/2<\/jats:sub>\n                    ), clearance, and volume of distribution at steady state (\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>ss<\/jats:sub>\n                    ) for the 15-mg\/kg, day 5 dose were 239 \u00b1 45 h\u00b7mg\/liter, 113 \u00b1 17 mg\/liter, 3 \u00b1 0.3 h, 1.1 \u00b1 0.1 ml\/min\/kg, and 0.24 \u00b1 0.04 liters\/kg, respectively. AEs were mild to moderate and rapidly resolved. No evidence of nephrotoxicity or ototoxicity was observed.\n                  <\/jats:p>","DOI":"10.1128\/aac.00624-11","type":"journal-article","created":{"date-parts":[[2011,9,13]],"date-time":"2011-09-13T02:41:38Z","timestamp":1315881698000},"page":"5874-5880","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":58,"title":["Pharmacokinetics and Safety of Single and Multiple Doses of ACHN-490 Injection Administered Intravenously in Healthy Subjects"],"prefix":"10.1128","volume":"55","author":[{"given":"Robert T.","family":"Cass","sequence":"first","affiliation":[{"name":"Achaogen Inc., South San Francisco, California 94080"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carter D.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Jasper Clinic, Inc., Kalamazoo, Michigan 49007"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy A.","family":"Havrilla","sequence":"additional","affiliation":[{"name":"Ardea Biosciences Inc., San Diego, California 92121"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth J.","family":"Tack","sequence":"additional","affiliation":[{"name":"Achaogen Inc., South San Francisco, California 94080"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie T.","family":"Borin","sequence":"additional","affiliation":[{"name":"Achaogen Inc., South San Francisco, California 94080"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Don","family":"Young","sequence":"additional","affiliation":[{"name":"Achaogen Inc., South San Francisco, California 94080"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon B.","family":"Bruss","sequence":"additional","affiliation":[{"name":"Medpace, Cincinnati, Ohio 45227"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00572-10"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/510079"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2010.09.004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.4.914"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.31.7.1054"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/520991"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2008.09.001"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00556-09"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.67.1.123"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.12.5.606"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq278"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq459"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01350-09"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/155.1.93"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.3.650"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/0885066610377968"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00862-10"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.7.1549"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.5.981"},{"key":"e_1_3_2_22_2","article-title":"Population pharmacokinetics of ACHN-490 injection in healthy subjects","author":"Van Wart S.","year":"2010","unstructured":"Van WartS.. 2010. Population pharmacokinetics of ACHN-490 injection in healthy subjects. Abstr. 48th Annu. Meet. Infect. Dis. Soc. Am., poster 209.","journal-title":"Abstr. 48th Annu. Meet. Infect. Dis. Soc. 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