{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T14:52:59Z","timestamp":1791125579118,"version":"4.1.0"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[1999,3,1]],"date-time":"1999-03-01T00:00:00Z","timestamp":920246400000},"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":[[1999,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Liposomal aminoglycosides have been shown to have activity against intracellular infections, such as those caused by\n            <jats:italic>Mycobacterium avium<\/jats:italic>\n            . Amikacin in small, low-clearance liposomes (MiKasome) also has curative and prophylactic efficacies against\n            <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n            and\n            <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n            . To develop appropriate dosing regimens for low-clearance liposomal amikacin, we studied the pharmacokinetics of liposomal amikacin in plasma, the level of exposure of plasma to free amikacin, and urinary excretion of amikacin after the administration of single-dose (20 mg\/kg of body weight) and repeated-dose (20 mg\/kg eight times at 48-h intervals) regimens in rhesus monkeys. The clearance of liposomal amikacin (single-dose regimen, 0.023 \u00b1 0.003 ml min\n            <jats:sup>\u22121<\/jats:sup>\n            kg\n            <jats:sup>\u22121<\/jats:sup>\n            ; repeated-dose regimen, 0.014 \u00b1 0.001 ml min\n            <jats:sup>\u22121<\/jats:sup>\n            kg\n            <jats:sup>\u22121<\/jats:sup>\n            ) was over 100-fold lower than the creatinine clearance (an estimate of conventional amikacin clearance). Half-lives in plasma were longer than those reported for other amikacin formulations and declined during the elimination phase following administration of the last dose (from 81.7 \u00b1 27 to 30.5 \u00b1 5 h). Peak and trough (48 h) levels after repeated dosing reached 728 \u00b1 72 and 418 \u00b1 60 \u03bcg\/ml, respectively. The levels in plasma remained &gt;180 \u03bcg\/ml for 6 days after the administration of the last dose. The free amikacin concentration in plasma never exceeded 17.4 \u00b1 1 \u03bcg\/ml and fell rapidly (half-life, 1.47 to 1.85 h) after the administration of each dose of liposomal amikacin. This and the low volume of distribution (45 ml\/kg) indicate that the amikacin in plasma largely remained sequestered in long-circulating liposomes. Less than half the amikacin was recovered in the urine, suggesting that the level of renal exposure to filtered free amikacin was reduced, possibly as a result of intracellular uptake or the metabolism of liposomal amikacin. Thus, low-clearance liposomal amikacin could be administered at prolonged (2- to 7-day) intervals to achieve high levels of exposure to liposomal amikacin with minimal exposure to free amikacin.\n          <\/jats:p>","DOI":"10.1128\/aac.43.3.503","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:34:19Z","timestamp":1539045259000},"page":"503-509","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Pharmacokinetics and Urinary Excretion of Amikacin in Low-Clearance Unilamellar Liposomes after a Single or Repeated Intravenous Administration in the Rhesus Monkey"],"prefix":"10.1128","volume":"43","author":[{"given":"Robert M.","family":"Fielding","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->NeXstar Pharmaceuticals, Inc., Boulder, Colorado,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotus","family":"Moon-Mcdermott","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->NeXstar Pharmaceuticals, Inc., Boulder, Colorado,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramilla O.","family":"Lewis","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->NeXstar Pharmaceuticals, Inc., Boulder, Colorado,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle J.","family":"Horner","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Sierra Biomedical, Inc. Sparks, Nevada2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0005-2736(91)90201-I","article-title":"Pharmacokinetics of stealth versus conventional liposomes: effect of dose.","volume":"1068","author":"Allen T. M.","year":"1991","unstructured":"Allen T. M. Hansen C. Pharmacokinetics of stealth versus conventional liposomes: effect of dose. Biochim. Biophys. Acta 1068 1991 133 141","journal-title":"Biochim. Biophys. Acta"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1023\/A:1012194721763","article-title":"Activation of the mononuclear phagocyte system by poloxamine 908: its implications for targeted drug delivery.","volume":"14","author":"Armstrong T. I.","year":"1997","unstructured":"Armstrong T. I. Moghimi S. M. Davis S. S. Illum L. Activation of the mononuclear phagocyte system by poloxamine 908: its implications for targeted drug delivery. Pharm. Res 14 1997 1629 1633","journal-title":"Pharm. Res"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/171.4.938"},{"key":"e_1_3_2_5_2","unstructured":"Benet\n              L. Z.\n              \u00d8ie\n              S.\n              Schwartz\n              J. B.\n          Design and optimization of dosage regimens; pharmacokinetic data.\n          The pharmacological basis of therapeutics\n          9th ed.\n              Hardman\n              J. G.\n          1996\n          McGraw-Hill Book Co.\n          New York N.Y"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.3.4.478"},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S0006-2952(96)00765-4","article-title":"Comparison of the effects of amikacin and kanamycins A and B on dimyristoylphosphatidylglycerol bilayers.","volume":"53","author":"Carrier D.","year":"1997","unstructured":"Carrier D. Chartrand N. Matar W. Comparison of the effects of amikacin and kanamycins A and B on dimyristoylphosphatidylglycerol bilayers. Biochem. Pharmacol. 53 1997 401 408","journal-title":"Biochem. Pharmacol."},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"18759","DOI":"10.1016\/S0021-9258(19)37026-7","article-title":"Association of blood proteins with large unilamellar liposomes in vivo.","volume":"267","author":"Chonn A.","year":"1992","unstructured":"Chonn A. Semple S. C. Cullis P. R. 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