{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:22:09Z","timestamp":1790338929393,"version":"4.1.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T00:00:00Z","timestamp":1559174400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T00:00:00Z","timestamp":1559174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["836041004"],"award-info":[{"award-number":["836041004"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pharm Res"],"published-print":{"date-parts":[[2019,8]]},"DOI":"10.1007\/s11095-019-2651-2","type":"journal-article","created":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T18:49:53Z","timestamp":1559242193000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Tobramycin Clearance Is Best Described by Renal Function Estimates in Obese and Non-obese Individuals: Results of a Prospective Rich Sampling Pharmacokinetic Study"],"prefix":"10.1007","volume":"36","author":[{"given":"Cornelis","family":"Smit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roeland E.","family":"Wasmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinus J.","family":"Wiezer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendricus P. A.","family":"van Dongen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan W.","family":"Mouton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger J. M.","family":"Br\u00fcggemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9893-4415","authenticated-orcid":false,"given":"Catherijne A. J.","family":"Knibbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,5,30]]},"reference":[{"key":"2651_CR1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1056\/NEJMoa1614362","volume":"377","author":"A Afshin","year":"2017","unstructured":"GBD 2015 Obesity Collaborators, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, et al. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017;377:13\u201327.","journal-title":"N Engl J Med"},{"key":"2651_CR2","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1080\/17425255.2018.1440287","volume":"14","author":"C Smit","year":"2018","unstructured":"Smit C, De Hoogd S, Br\u00fcggemann RJM, Knibbe CAJ. Obesity and drug pharmacology: a review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters. Expert Opin Drug Metab Toxicol. 2018;14:275\u201385.","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"2651_CR3","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/S0891-5520(03)00057-6","volume":"17","author":"J Turnidge","year":"2003","unstructured":"Turnidge J. Pharmacodynamics and dosing of aminoglycosides. Infect Dis Clin N Am. 2003;17:503\u201328.","journal-title":"Infect Dis Clin N Am"},{"key":"2651_CR4","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.diagmicrobio.2005.02.011","volume":"52","author":"JW Mouton","year":"2005","unstructured":"Mouton JW, Jacobs N, Tiddens H, Horrevorts AM. Pharmacodynamics of tobramycin in patients with cystic fibrosis. Diagn Microbiol Infect Dis. 2005;52:123\u20137.","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2651_CR5","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1086\/518137","volume":"45","author":"GL Drusano","year":"2007","unstructured":"Drusano GL, Ambrose PG, Bhavnani SM, Bertino JS, Nafziger AN, Louie A. Back to the future: using aminoglycosides again and how to dose them optimally. Clin Infect Dis. 2007;45:753\u201360.","journal-title":"Clin Infect Dis"},{"key":"2651_CR6","unstructured":"EUCAST. Gentamicin: Rationale for the EUCAST clinical breakpoint (version 1.2). 2009."},{"key":"2651_CR7","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.diagmicrobio.2013.10.011","volume":"78","author":"MP Pai","year":"2014","unstructured":"Pai MP, Rodvold KA. Aminoglycoside dosing in patients by kidney function and area under the curve: the Sawchuk-Zaske dosing method revisited in the era of obesity. Diagn Microbiol Infect Dis. 2014;78:178\u201387.","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2651_CR8","unstructured":"European Committee on Antimicrobial Susceptibility Testing (EUCAST). Data from the EUCAST MIC distribution website [Internet]. [cited 2019 Apr 4]. Available from: \nhttps:\/\/mic.eucast.org\/\n\n. Accessed 4 April 2019"},{"key":"2651_CR9","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/0140-6736(93)90137-6","volume":"341","author":"JM Prins","year":"1993","unstructured":"Prins JM, B\u00fcller HR, Kuijper EJ, Tange RA, Speelman P. Once versus thrice daily gentamicin in patients with serious infections. Lancet. 1993;341:335\u20139.","journal-title":"Lancet."},{"key":"2651_CR10","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1128\/AAC.43.7.1549","volume":"43","author":"MJ Rybak","year":"1999","unstructured":"Rybak MJ, Abate BJ, Kang SL, Ruffing MJ, Lerner SA, Drusano GL. Prospective evaluation of the effect of an aminoglycoside dosing regimen on rates of observed nephrotoxicity and ototoxicity. Antimicrob Agents Chemother. 1999;43:1549\u201355.","journal-title":"Antimicrob Agents Chemother"},{"key":"2651_CR11","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1007\/BF00542215","volume":"24","author":"LA Bauer","year":"1983","unstructured":"Bauer LA, Edwards WAD, Dellinger EP, Simonowitz DA. Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients. Eur J Clin Pharmacol. 1983;24:643\u20137.","journal-title":"Eur J Clin Pharmacol"},{"key":"2651_CR12","first-page":"2125","volume":"51","author":"WG Leader","year":"1994","unstructured":"Leader WG, Tsubaki T, Chandler MH. Creatinine-clearance estimates for predicting gentamicin pharmacokinetic values in obese patients. Am J Hosp Pharm. 1994;51:2125\u201330.","journal-title":"Am J Hosp Pharm"},{"key":"2651_CR13","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1093\/infdis\/138.4.499","volume":"138","author":"SN Schwartz","year":"1978","unstructured":"Schwartz SN, Pazin GJ, Lyon JA, Ho M, Pasculle AW. A controlled investigation of the pharmacokinetics of gentamicin and tobramycin in obese subjects. J Infect Dis. 1978;138:499\u2013505.","journal-title":"J Infect Dis"},{"key":"2651_CR14","first-page":"549","volume":"18","author":"S Korsager","year":"1980","unstructured":"Korsager S. Administration of gentamicin to obese patients. Int J Clin Pharmacol Ther Toxicol. 1980;18:549\u201353.","journal-title":"Int J Clin Pharmacol Ther Toxicol"},{"key":"2651_CR15","doi-asserted-by":"publisher","first-page":"4006","DOI":"10.1128\/AAC.00174-11","volume":"55","author":"MP Pai","year":"2011","unstructured":"Pai MP, Nafziger AN, Bertino JS. Simplified estimation of aminoglycoside pharmacokinetics in underweight and obese adult patients. Antimicrob Agents Chemother. 2011;55:4006\u201311.","journal-title":"Antimicrob Agents Chemother"},{"key":"2651_CR16","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1002\/j.1552-4604.1981.tb01769.x","volume":"21","author":"I Sketris","year":"1981","unstructured":"Sketris I, Lesar T, Zaske DE, Cipolle RJ. Effect of obesity on gentamicin pharmacokinetics. J Clin Pharmacol. 1981;21:288\u201393.","journal-title":"J Clin Pharmacol"},{"issue":"10","key":"2651_CR17","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1007\/s40262-019-00762-4","volume":"58","author":"Cornelis Smit","year":"2019","unstructured":"Smit C, Wasmann RE, Goulooze SC, Hazebroek EJ, van Dongen HPA, Burgers DMT, et al. A prospective clinical study characterizing the influence of morbid obesity on the pharmacokinetics of gentamicin: towards individualized dosing in obese patients. Clin Pharmacokinet 2019; Apr 24. \nhttps:\/\/doi.org\/10.1007\/s40262-019-00762-4\n\n.","journal-title":"Clinical Pharmacokinetics"},{"key":"2651_CR18","doi-asserted-by":"publisher","first-page":"642","DOI":"10.2146\/ajhp080200","volume":"66","author":"JA Demirovic","year":"2009","unstructured":"Demirovic JA, Pai AB, Pai MP. Estimation of creatinine clearance in morbidly obese patients. Am J Health Syst Pharm. 2009;66:642\u20138.","journal-title":"Am J Health Syst Pharm"},{"key":"2651_CR19","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.2165\/00003088-200544100-00004","volume":"44","author":"S Janmahasatian","year":"2005","unstructured":"Janmahasatian S, Duffull SB, Ash S, Ward LC, Byrne NM, Green B. Quantification of lean bodyweight. Clin Pharmacokinet. 2005;44:1051\u201365.","journal-title":"Clin Pharmacokinet"},{"key":"2651_CR20","volume-title":"NONMEM user\u2019s guide","author":"SL Beal","year":"1999","unstructured":"Beal SL, Sheiner LB, Boeckmann A. NONMEM user\u2019s guide. San Francisco: University of California; 1999."},{"key":"2651_CR21","doi-asserted-by":"publisher","first-page":"e50","DOI":"10.1038\/psp.2013.24","volume":"2","author":"RJ Keizer","year":"2013","unstructured":"Keizer RJ, Karlsson MO, Hooker A. Modeling and simulation workbench for NONMEM: tutorial on Pirana, PsN, and Xpose. CPT Pharmacometrics Syst Pharmacol. 2013;2:e50.","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"key":"2651_CR22","unstructured":"R Core Team. R: A language and environment for statistical computing. 2015."},{"key":"2651_CR23","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1023\/A:1012299115260","volume":"28","author":"SL Beal","year":"2001","unstructured":"Beal SL. Ways to fit a PK model with some data below the quantification limit. J Pharmacokinet Pharmacodyn. 2001;28:481\u2013504.","journal-title":"J Pharmacokinet Pharmacodyn"},{"key":"2651_CR24","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1007\/s11095-013-1197-y","volume":"31","author":"RFW De Cock","year":"2014","unstructured":"De Cock RFW, Allegaert K, Sherwin CMT, Nielsen EI, De Hoog M, Van Den Anker JN, et al. A neonatal amikacin covariate model can be used to predict ontogeny of other drugs eliminated through glomerular filtration in neonates. Pharm Res. 2014;31:754\u201367.","journal-title":"Pharm Res"},{"key":"2651_CR25","doi-asserted-by":"publisher","first-page":"2643","DOI":"10.1007\/s11095-014-1361-z","volume":"31","author":"RFW De Cock","year":"2014","unstructured":"De Cock RFW, Allegaert K, Brussee JM, Sherwin CMT, Mulla H, De Hoog M, et al. Simultaneous pharmacokinetic modeling of gentamicin, tobramycin and vancomycin clearance from neonates to adults: towards a semi-physiological function for maturation in glomerular filtration. Pharm Res. 2014;31:2643\u201354.","journal-title":"Pharm Res"},{"key":"2651_CR26","doi-asserted-by":"publisher","first-page":"R204","DOI":"10.1186\/cc2872","volume":"8","author":"R Bellomo","year":"2004","unstructured":"Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, Acute Dialysis Quality Initiative workgroup. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the second international consensus conference of the acute Dialysis quality initiative (ADQI) group. Crit Care. 2004;8:R204\u201312.","journal-title":"Crit Care"},{"key":"2651_CR27","unstructured":"Committee for Medicinal Products for human use (CHMP) - European medicines agency (EMA). Guideline on the investigation of bioequivalence - CPMP\/EWP\/QWP\/1401\/98 Rev. 1. 2010."},{"key":"2651_CR28","unstructured":"European Medicines Agency (EMA). Guideline on the use of pharmacokinetics and pharmacodynamics in the development of antimicrobial medicinal products. 2016."},{"key":"2651_CR29","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1111\/imj.12684","volume":"45","author":"AKH Lim","year":"2015","unstructured":"Lim AKH, Mathanasenarajah G, Larmour I. Assessment of aminoglycoside dosing and estimated glomerular filtration rate in determining gentamicin and tobramycin area under the curve and clearance. Intern Med J. 2015;45:319\u201329.","journal-title":"Intern Med J"},{"key":"2651_CR30","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1128\/AAC.3.4.469","volume":"3","author":"KG Naber","year":"1973","unstructured":"Naber KG, Westenfelder SR, Madsen PO. Pharmacokinetics of the aminoglycoside antibiotic tobramycin in humans. Antimicrob Agents Chemother. 1973;3:469\u201373.","journal-title":"Antimicrob Agents Chemother"},{"key":"2651_CR31","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1111\/bcp.12817","volume":"81","author":"A Bouquegneau","year":"2016","unstructured":"Bouquegneau A, Vidal-Petiot E, Moranne O, Mariat C, Boffa J-J, Vrtovsnik F, et al. Creatinine-based equations for the adjustment of drug dosage in an obese population. Br J Clin Pharmacol. 2016;81:349\u201361.","journal-title":"Br J Clin Pharmacol"},{"key":"2651_CR32","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1159\/000329547","volume":"4","author":"G Wuerzner","year":"2011","unstructured":"Wuerzner G, Bochud M, Giusti V, Burnier M. Measurement of glomerular filtration rate in obese patients: pitfalls and potential consequences on drug therapy. Obes Facts. 2011;4:238\u201343.","journal-title":"Obes Facts"},{"key":"2651_CR33","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1053\/j.ackd.2010.05.010","volume":"17","author":"MP Pai","year":"2010","unstructured":"Pai MP. Estimating the glomerular filtration rate in obese adult patients for drug dosing. Adv Chronic Kidney Dis. 2010;17:53\u201362.","journal-title":"Adv Chronic Kidney Dis"},{"key":"2651_CR34","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1111\/j.1440-1797.2006.00560.x","volume":"11","author":"WH Lim","year":"2006","unstructured":"Lim WH, Lim EM, McDonald S. Lean body mass-adjusted Cockcroft and gault formula improves the estimation of glomerular filtration rate in subjects with normal-range serum creatinine. Nephrology. 2006;11:250\u20136.","journal-title":"Nephrology."},{"key":"2651_CR35","doi-asserted-by":"publisher","first-page":"5573","DOI":"10.1128\/AAC.00907-16","volume":"60","author":"Z Gai","year":"2016","unstructured":"Gai Z, Visentin M, Hiller C, Krajnc E, Li T, Zhen J, et al. Organic cation transporter 2 overexpression may confer an increased risk of Gentamicin-induced nephrotoxicity. Antimicrob Agents Chemother. 2016;60:5573\u201380.","journal-title":"Antimicrob Agents Chemother"},{"key":"2651_CR36","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1208\/s12248-013-9460-z","volume":"15","author":"H Yoon","year":"2013","unstructured":"Yoon H, Cho H-Y, Yoo H-D, Kim S-M, Lee Y-B. Influences of organic cation transporter polymorphisms on the population pharmacokinetics of metformin in healthy subjects. AAPS J. 2013;15:571\u201380.","journal-title":"AAPS J"},{"key":"2651_CR37","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/s40272-018-0293-1","volume":"20","author":"A van Rongen","year":"2018","unstructured":"van Rongen A, van der Aa MP, Matic M, van Schaik RHN, Deneer VHM, van der Vorst MM, et al. Increased metformin clearance in overweight and obese adolescents: a pharmacokinetic substudy of a randomized controlled trial. Paediatr Drugs. 2018;20:365\u201374.","journal-title":"Paediatr Drugs"},{"key":"2651_CR38","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1128\/AAC.19.5.859","volume":"19","author":"JJ Schentag","year":"1981","unstructured":"Schentag JJ, Plaut ME, Cerra FB. Comparative nephrotoxicity of gentamicin and tobramycin: pharmacokinetic and clinical studies in 201 patients. Antimicrob Agents Chemother. 1981;19:859\u201366.","journal-title":"Antimicrob Agents Chemother"},{"key":"2651_CR39","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1086\/514505","volume":"25","author":"R Wurtz","year":"1997","unstructured":"Wurtz R, Itokazu G, Rodvold K. Antimicrobial dosing in obese patients. Clin Infect Dis. 1997;25:112\u20138.","journal-title":"Clin Infect Dis"},{"key":"2651_CR40","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1592\/phco.27.8.1081","volume":"27","author":"MP Pai","year":"2007","unstructured":"Pai MP, Bearden DT. Antimicrobial dosing considerations in obese adult patients. Pharmacotherapy. 2007;27:1081\u201391.","journal-title":"Pharmacotherapy."},{"key":"2651_CR41","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1007\/s00228-014-1680-3","volume":"70","author":"L Nezic","year":"2014","unstructured":"Nezic L, Derungs A, Bruggisser M, Tschudin-Sutter S, Kr\u00e4henb\u00fchl S, Haschke M. Therapeutic drug monitoring of once daily aminoglycoside dosing: comparison of two methods and investigation of the optimal blood sampling strategy. Eur J Clin Pharmacol. 2014;70:829\u201337.","journal-title":"Eur J Clin Pharmacol"}],"updated-by":[{"DOI":"10.1007\/s11095-020-2756-7","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T00:00:00Z","timestamp":1578528000000}}],"container-title":["Pharmaceutical Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11095-019-2651-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11095-019-2651-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11095-019-2651-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T19:08:05Z","timestamp":1590692885000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11095-019-2651-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,30]]},"references-count":41,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["2651"],"URL":"https:\/\/doi.org\/10.1007\/s11095-019-2651-2","relation":{"correction":[{"id-type":"doi","id":"10.1007\/s11095-020-2756-7","asserted-by":"object"}]},"ISSN":["0724-8741","1573-904X"],"issn-type":[{"value":"0724-8741","type":"print"},{"value":"1573-904X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,30]]},"assertion":[{"value":"7 April 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2020","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"There was a mistake in the units of CL and Q, and in the parentheses of the formula for CL in the final model in Table 2. The corrected Table appears below.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"112"}}