{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:46:46Z","timestamp":1782280006952,"version":"3.54.5"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The area under the concentration\u2012time curve (AUC) is recognized as the therapeutic drug monitoring index of polymyxin B. The two-point method, which is based on peak and trough concentrations, is recommended for AUC estimation. However, its accuracy needs to be fully elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A Monte Carlo simulation study was performed on published population pharmacokinetic (PPK) models. A series of plasma concentrations at steady state were simulated for each scenario. The performance of the two-point method was evaluated via mean absolute percent error (MAPE) and root mean square error (RMSE), with acceptable performance limits defined as \u226415% for the MAPE and \u226420% for the RMSE. Additionally, variations in infusion duration, body weight, and creatinine clearance were also investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the one-compartment model, the two-point method exhibits excellent predictive performance, characterized by both the MAPE and RMSE &amp;lt; 15%. For multicompartment models, prolonging the infusion duration markedly improved the accuracy of the two-point method, as demonstrated by a decrease in the average MAPE from 30.2% to 7.78% and in the average RMSE from 35.5% to 9.12% when comparing infusion durations of 0.5\u00a0h and 2\u00a0h. Body weight and creatinine clearance had limited influences on estimation accuracy in most models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The two-point method, which is based on peak and trough concentrations, represents a strong pharmacokinetic rationale and generate a testable hypothesis for the clinical application for estimating the AUC of polymyxin B. We suggest prolonging the infusion duration to ensure estimation accuracy in different patient settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1838789","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:51:55Z","timestamp":1782276715000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Can the two-point method based on peak and trough concentrations accurately estimate the area under the curve of polymyxin B? A Monte Carlo simulation study"],"prefix":"10.3389","volume":"17","author":[{"given":"Jieqiong","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]},{"name":"Research Center for Clinical Pharmacy, College of Pharmaceutical Science, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Affiliated Xiaoshan Hospital, Hangzhou Normal University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenwei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]},{"name":"Research Center for Clinical Pharmacy, College of Pharmaceutical Science, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1007\/s00134-020-06050-1","article-title":"Antimicrobial therapeutic drug monitoring in critically ill adult patients: A position paper","volume":"46","author":"Abdul-Aziz","year":"2020","journal-title":"Intensive Care Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1019411","DOI":"10.3389\/fphar.2022.1019411","article-title":"Population pharmacokinetic analysis, renal safety, and dosing optimization of polymyxin B in lung transplant recipients with pneumonia: a prospective study","volume":"13","author":"Cai","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s00228-020-02986-x","article-title":"Estimation of the area under concentration-time curve of polymyxin B based on limited sampling concentrations in Chinese patients with severe pneumonia","volume":"77","author":"Chen","year":"2021","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e00792","DOI":"10.1128\/AAC.00792-21","article-title":"Pharmacokinetics of polymyxin B in hospitalized adults with cystic fibrosis","volume":"65","author":"Crass","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"B3","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.jgar.2020.12.026","article-title":"Clinical use of intravenous polymyxin B for the treatment of patients with multidrug-resistant gram-negative bacterial infections: An evaluation of the current evidence","volume":"24","author":"Falagas","year":"2021","journal-title":"J. Glob. Antimicrob. Resist"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1016\/j.cmi.2023.05.018","article-title":"A population pharmacokinetic model of polymyxin B based on prospective clinical data to inform dosing in hospitalized patients","volume":"29","author":"Hanafin","year":"2023","journal-title":"Clin. Microbiol. Infect."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e01493","DOI":"10.1128\/AAC.01493-17","article-title":"Population pharmacokinetics of intravenous polymyxin B from clinical samples","volume":"62","author":"Kubin","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"B4","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1093\/jac\/dkx409","article-title":"Pharmacokinetics\/Pharmacodynamics of systemically administered polymyxin B against Klebsiella pneumoniae in mouse thigh and lung infection models","volume":"73","author":"Landersdorfer","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"B5","doi-asserted-by":"publisher","first-page":"727170","DOI":"10.3389\/fphar.2021.727170","article-title":"Population pharmacokinetics of polymyxin B and dosage optimization in renal transplant patients","volume":"12","author":"Li","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1007\/s00228-021-03193-y","article-title":"External evaluation of published population pharmacokinetic models of polymyxin B","volume":"77","author":"Li","year":"2021","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2323","DOI":"10.3390\/pharmaceutics14112323","article-title":"Evaluation and validation of the limited sampling strategy of polymyxin B in patients with multidrug-resistant gram-negative infection","volume":"14","author":"Li","year":"2022","journal-title":"Pharmaceutics"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1122310","DOI":"10.3389\/fphar.2023.1122310","article-title":"Population pharmacokinetic analysis and dosing optimization of polymyxin B in critically ill patients","volume":"14","author":"Liang","year":"2023","journal-title":"Front. Pharmacol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.jinf.2021.01.006","article-title":"Acute toxicity is a dose-limiting factor for intravenous polymyxin B: A safety and pharmacokinetic study in healthy Chinese subjects","volume":"82","author":"Liu","year":"2021","journal-title":"J. Infect."},{"key":"B9","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1631\/jzus.B2200466","article-title":"Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B, endorsed by the infection and chemotherapy committee of the shanghai medical association and the therapeutic drug monitoring committee of the Chinese pharmacological society","volume":"24","author":"Liu","year":"2023","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1370040","DOI":"10.3389\/fphar.2024.1370040","article-title":"Is it time to recommend AUC-based vancomycin therapeutic drug monitoring only? A cross-sectional survey in China","volume":"15","author":"Liu","year":"","journal-title":"Front. Pharmacol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1080\/00498254.2024.2370051","article-title":"Three methods to optimise polymyxin B dosing using estimated AUC after first dose: validation with the data generated by Monte Carlo simulation","volume":"54","author":"Liu","year":"","journal-title":"Xenobiotica"},{"key":"B39","doi-asserted-by":"publisher","first-page":"106214","DOI":"10.1016\/j.ejps.2022.106214","article-title":"Population pharmacokinetics of polymyxin B and dosage strategy in critically ill patients with\/without continuous renal replacement therapy","volume":"175","author":"Luo","year":"2022","journal-title":"Eur. J. Pharm. Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1002\/cpt.981","article-title":"Population pharmacokinetics of polymyxin B","volume":"104","author":"Manchandani","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e01475","DOI":"10.1128\/AAC.01475-17","article-title":"Population pharmacokinetics of polymyxin B in acutely ill adult patients","volume":"62","author":"Miglis","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"B12","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"B13","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1124\/pharmrev.120.000020","article-title":"Rescuing the last-line polymyxins: Achievements and challenges","volume":"73","author":"Nang","year":"2021","journal-title":"Pharmacol. Rev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"24","DOI":"10.3390\/antibiotics8010024","article-title":"Polymyxin acute kidney injury: Dosing and other strategies to reduce toxicity","volume":"8","author":"Nation","year":"2019","journal-title":"Antibiot. basel, Switz."},{"key":"B15","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1128\/AAC.01653-13","article-title":"Are vancomycin trough concentrations adequate for optimal dosing?","volume":"58","author":"Neely","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"B16","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1093\/jac\/dkad012","article-title":"Population pharmacokinetics and limited sampling strategies of polymyxin B in critically ill patients","volume":"78","author":"Pi","year":"2023","journal-title":"J. Antimicrob. Chemother."},{"key":"B37","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1093\/cid\/cit334","article-title":"Population pharmacokinetics of intravenous polymyxin B in critically ill patients: Implications for selection of dosage regimens","volume":"57","author":"Sandri","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"ciad428","DOI":"10.1093\/cid\/ciad428","article-title":"Infectious diseases society of America 2023 guidance on the treatment of antimicrobial resistant gram-negative infections","author":"Tamma","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1186\/s13054-023-04448-z","article-title":"Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: A real-world prospective study","volume":"27","author":"Tang","year":"2023","journal-title":"Crit. Care"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e0244966","DOI":"10.1371\/journal.pone.0244966","article-title":"Clinical and pharmacokinetic\/dynamic outcomes of prolonged infusions of beta-lactam antimicrobials: An overview of systematic reviews","volume":"16","author":"Thabet","year":"2021","journal-title":"PLOS ONE"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e01040-24","DOI":"10.1128\/aac.01040-24","article-title":"Comparing two-sample log-linear exposure estimation with bayesian model-informed precision dosing of tobramycin in adult patients with cystic fibrosis","volume":"69","author":"Tong","year":"2025","journal-title":"Antimicrob. Agents Chemother."},{"key":"B21","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1002\/phar.2209","article-title":"International consensus guidelines for the optimal use of the polymyxins: endorsed by the American college of clinical pharmacy (ACCP), european society of clinical microbiology and infectious diseases (ESCMID), infectious diseases society of America (IDSA), international society for anti-infective pharmacology (ISAP), society of critical care medicine (SCCM), and society of infectious diseases pharmacists (SIDP)","volume":"39","author":"Tsuji","year":"2019","journal-title":"Pharmacotherapy"},{"key":"B22","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1093\/jac\/dkad022","article-title":"Pharmacokinetic and pharmacodynamic properties of polymyxin B in Escherichia coli and Klebsiella pneumoniae murine infection models","volume":"78","author":"van der Meijden","year":"2023","journal-title":"J. Antimicrob. Chemother."},{"key":"B23","doi-asserted-by":"publisher","first-page":"829","DOI":"10.3389\/fphar.2020.00829","article-title":"Population pharmacokinetics and limited sampling strategy for therapeutic drug monitoring of polymyxin B in Chinese patients with multidrug-resistant gram-negative bacterial infections","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"754844","DOI":"10.3389\/fphar.2021.754844","article-title":"Population pharmacokinetics of polymyxin B in obese patients for resistant gram-negative infections","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"106693","DOI":"10.1016\/j.ijantimicag.202","article-title":"Pharmacokinetics and pharmacodynamics of polymyxin B and proposed dosing regimens in elderly patients with multi-drug-resistant gram-negative bacterial infections","volume":"60","author":"Wang","year":"2022","journal-title":"Int. J. Antimicrob. Agents."},{"key":"B24","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1007\/s00228-024-03666-w","article-title":"Pharmacokinetics of polymyxin B in different populations: A systematic review","volume":"80","author":"Wang","year":"2024","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"B25","volume-title":"Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report 2022","year":"2022"},{"key":"B26","doi-asserted-by":"publisher","first-page":"672543","DOI":"10.3389\/fphar.2022.672543","article-title":"Polymyxin B-Associated nephrotoxicity and its predictors: a retrospective study in carbapenem-resistant gram-negative bacterial infections","volume":"13","author":"Wu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1186\/s13054-022-04195-7","article-title":"An area under the concentration\u2013time curve threshold as a predictor of efficacy and nephrotoxicity for individualizing polymyxin B dosing in patients with carbapenem-resistant gram-negative bacteria","volume":"26","author":"Yang","year":"2022","journal-title":"Crit. Care"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1111\/jcpt.13711","article-title":"The population pharmacokinetics and dose optimization of polymyxin B in critically ill patients with or without extracorporeal membrane oxygenation","volume":"47","author":"Ye","year":"2022","journal-title":"Clin. Pharm. Ther."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1111\/bcp.14576","article-title":"Population pharmacokinetic and optimization of polymyxin B dosing in adult patients with various renal functions","volume":"87","author":"Yu","year":"2021","journal-title":"Brit. J. Clinical. Pharma."},{"key":"B29","doi-asserted-by":"publisher","first-page":"975066","DOI":"10.3389\/fphar.2022.975066","article-title":"Pharmacokinetics\/Pharmacodynamics of polymyxin B in patients with bloodstream infection caused by carbapenem-resistant klebsiella pneumoniae","volume":"13","author":"Yu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e01859-24","DOI":"10.1128\/aac.01859-24","article-title":"Clinical outcomes and pharmacokinetics\/pharmacodynamics of intravenous polymyxin B treatment for various site carbapenem-resistant gram-negative bacterial infections: A prospective observational multicenter study","volume":"69","author":"Yu","year":"2025","journal-title":"Antimicrob. Agents Chemother."},{"key":"B31","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1007\/s40262-025-01488-2","article-title":"A systematic review of pharmacokinetic studies of colistin and polymyxin B in adult populations","volume":"64","author":"Zamri","year":"2025","journal-title":"Clin. Pharmacokinet."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1838789\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:52:00Z","timestamp":1782276720000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1838789\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":43,"alternative-id":["10.3389\/fphar.2026.1838789"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1838789","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]},"article-number":"1838789"}}