{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T23:23:15Z","timestamp":1781220195550,"version":"3.54.1"},"reference-count":17,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T00:00:00Z","timestamp":1588636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Systemic aminoglycosides remain a cornerstone of treatment for cystic fibrosis (CF) pulmonary exacerbations (PEx); however, the impact of aminoglycoside pharmacokinetics (PK) on outcomes is not well defined in adult CF patients. Our objective was to assess the impact of increasing PK exposures on the clinical outcomes of PEx treatment in adult CF patients receiving high\u2010dose and standard\u2010dose extended\u2010interval aminoglycosides.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a retrospective study of adult CF patients treated with an intravenous aminoglycoside for a PEx. Serum amikacin, gentamicin, and tobramycin levels and forced expiratory volume over 1 second (FEV<jats:sub>1<\/jats:sub>) data were used to evaluate exposure\u2010response relationships. PK parameters were estimated using a Bayesian approach to obtain area under the curve (AUC)<jats:sub>0\u201324 hr<\/jats:sub>, maximum concentration (C<jats:sub>max0\u201324 hr<\/jats:sub>), and minimum concentration (Cmin<jats:sub>0\u201324 hr<\/jats:sub>) estimates. The primary efficacy end point was a 90% recovery of baseline FEV<jats:sub>1<\/jats:sub> by 30\u00a0days posttreatment. Toxicity included signs or symptoms of ototoxicity, vestibular toxicity, or renal toxicity. Multivariate linear mixed\u2010effects models of FEV<jats:sub>1<\/jats:sub> were used for exposure\u2010response analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study included 51 patients who contributed 188 FEV<jats:sub>1<\/jats:sub> observations. There were 3.0\u00a0\u00b1\u00a01.7 (mean\u00a0\u00b1\u00a0SD) aminoglycoside concentrations per patient. The mean AUC<jats:sub>0\u201324 hr<\/jats:sub>, C<jats:sub>max0\u201324 hr<\/jats:sub>, and C<jats:sub>min0\u201324 hr<\/jats:sub> across all agents and patients were 156\u00a0\u00b1\u00a096\u00a0mg*hr\/L, 29.9\u00a0\u00b1\u00a012.7\u00a0mg\/L, and 0.35\u00a0\u00b1\u00a00.66\u00a0mg\/L, respectively. A total of 42 amikacin\u2010, gentamicin\u2010, or tobramycin\u2010treated patients contributed to the efficacy analysis, of whom 85.7% experienced recovery posttreatment. Of the 51 included patients, 6 (11.8%) experienced seven toxicity events. In exploratory exposure\u2010response analyses, neither AUC<jats:sub>0\u201324 hr<\/jats:sub> nor C<jats:sub>max0\u201324 hr<\/jats:sub> was associated with FEV<jats:sub>1<\/jats:sub> values after adjusting for clinical covariates and baseline FEV<jats:sub>1<\/jats:sub>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Increasing aminoglycoside AUC<jats:sub>0\u201324 hr<\/jats:sub> and C<jats:sub>max0\u201324 hr<\/jats:sub> were not associated with FEV<jats:sub>1<\/jats:sub> during PEx treatment. Although individualizing aminoglycoside dosing in adult CF patients is necessary to minimize toxicity risk, more work is needed to define optimally safe and effective dosing strategies for this population.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2399","type":"journal-article","created":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T13:13:35Z","timestamp":1586265215000},"page":"584-591","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring the Relationship between FEV<sub>1<\/sub> Loss and Recovery and Aminoglycoside Pharmacokinetics in Adult Patients with Cystic Fibrosis: Implications for Clinical Dosing Strategies"],"prefix":"10.1002","volume":"40","author":[{"given":"Brian M.","family":"Hoff","sequence":"first","affiliation":[{"name":"Department of Pharmacy Northwestern Memorial Hospital Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1091-6130","authenticated-orcid":false,"given":"Marc H.","family":"Scheetz","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Northwestern Memorial Hospital Chicago Illinois"},{"name":"Department of Pharmacy Practice Midwestern University Chicago College of Pharmacy Downers Grove Illinois"},{"name":"Pharmacometrics Center of Excellence Midwestern University Chicago College of Pharmacy Downers Grove Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manu","family":"Jain","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Medicine Northwestern University Feinberg School of Medicine Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne F.","family":"Cullina","sequence":"additional","affiliation":[{"name":"Ann and Robert H. Lurie Children\u2019s Hospital Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0018-5434","authenticated-orcid":false,"given":"Nathaniel J.","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Northwestern Memorial Hospital Chicago Illinois"},{"name":"Department of Pharmacy Practice Midwestern University Chicago College of Pharmacy Downers Grove Illinois"},{"name":"Pharmacometrics Center of Excellence Midwestern University Chicago College of Pharmacy Downers Grove Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2014-206750"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.21374"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200812-1845PP"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00539-13"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2193"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/518751"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/591453"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.159.1.9712108"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200512-1919OC"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2015.08.042"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc5713"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e318161a38c"},{"key":"e_1_2_6_15_1","first-page":"576","volume-title":"Basic clinical pharmacokinetics","author":"Winter ME","year":"2003"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02355-14"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-53759-1"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(01)80103-X"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fphar.2399","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.2399","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/phar.2399","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.2399","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T10:35:15Z","timestamp":1761042915000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.2399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,5]]},"references-count":17,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1002\/phar.2399"],"URL":"https:\/\/doi.org\/10.1002\/phar.2399","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,5]]},"assertion":[{"value":"2020-01-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}