{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T06:39:24Z","timestamp":1781332764816,"version":"3.54.1"},"reference-count":27,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,6,19]],"date-time":"2021-06-19T00:00:00Z","timestamp":1624060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100010804","name":"Faculty of Medicine, Prince of Songkla University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Levofloxacin is considered a key component of a multidrug\u2010resistant tuberculosis (MDR\u2010TB) regimen. However, there is considerable concern regarding the subtherapeutic concentrations of the currently used doses and the development of drug resistance. Therefore, this study aimed to describe the population pharmacokinetics (PPK) of oral levofloxacin in healthy volunteers and to evaluate the probability of target attainment (PTA) in an attempt to optimize the dosing regimens for MDR\u2010TB therapy. Data of levofloxacin in healthy volunteers from a previous study were used to construct a PPK model. Monte Carlo simulations were performed to derive the PTAs of various regimens. A two\u2010compartment model with linear elimination and transit absorption compartments best described the pharmacokinetics (PK) of levofloxacin. The estimated PK parameters (interindividual variability, %) were: apparent clearance 8.32\u00a0L\u00a0h<jats:sup>\u22121<\/jats:sup> (22.6%), apparent central volume of distribution 35.8\u00a0L (45.2%), apparent peripheral volume of distribution 39.7\u00a0L, intercompartmental clearance 40.6\u00a0L\u00a0h<jats:sup>\u22121<\/jats:sup> (43.8%), absorption rate constant 7.45\u00a0h<jats:sup>\u22121<\/jats:sup> (150%), mean absorption transit time 0.355\u00a0h (52.4%), and total number of transit compartments 6.01 (131.9%). Monte Carlo simulations using levofloxacin 750\u20131000\u00a0mg yielded a probability of achieving a target free area under the concentration\u2013time curve\/minimum inhibitory concentration (MIC) of 100 at greater than 90% for <jats:italic>Mycobacterium tuberculosis<\/jats:italic> with an MIC &lt; 0.5\u00a0mg L<jats:sup>\u22121<\/jats:sup>, while a dose of 1500\u00a0mg was required for strains with an MIC of 1\u00a0mg L<jats:sup>\u22121<\/jats:sup>. A higher dose of levofloxacin might be needed to treat tuberculosis. However, further studies on the efficacy and safety of this dose are needed to confirm our findings.<\/jats:p>","DOI":"10.1002\/bdd.2294","type":"journal-article","created":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T01:40:32Z","timestamp":1623462032000},"page":"329-337","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Population pharmacokinetics of oral levofloxacin in healthy volunteers and dosing optimization for multidrug\u2010resistant tuberculosis therapy"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6169-0039","authenticated-orcid":false,"given":"Apinya","family":"Boonpeng","sequence":"first","affiliation":[{"name":"Division of Pharmacy Practice Department of Pharmaceutical Care School of Pharmaceutical Sciences University of Phayao  Muang Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8411-1407","authenticated-orcid":false,"given":"Sutep","family":"Jaruratanasirikul","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine Faculty of Medicine Prince of Songkla University  Hat Yai Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thitima","family":"Wattanavijitkul","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice Faculty of Pharmaceutical Sciences Chulalongkorn University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monchana","family":"Nawakitrangsan","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine Faculty of Medicine Prince of Songkla University  Hat Yai Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maseetoh","family":"Samaeng","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine Faculty of Medicine Prince of Songkla University  Hat Yai Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00341-15"},{"issue":"3","key":"e_1_2_7_3_1","first-page":"123","article-title":"Diagnostic and prognostic value of serum albumin for tuberculosis in HIV infected patients eligible for antiretroviral therapy: Datafrom an HIV cohort study in India","volume":"3","author":"Alvarez\u2010Uria G.","year":"2013","journal-title":"BioImpacts"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02134-16"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.23.7.881.32730"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy611"},{"key":"e_1_2_7_7_1","volume-title":"Data from the EUCAST MIC distribution website","author":"European Committee on Antimicrobial Susceptibility Testing","year":"2020"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199732020-00002"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw164"},{"key":"e_1_2_7_10_1","volume-title":"Levofloxacin tablets: Highlights of prescribing information","author":"Janssen Pharmaceutical Companies","year":"2020"},{"issue":"8","key":"e_1_2_7_11_1","first-page":"886","article-title":"Population pharmacokinetics and pharmacodynamics modeling of oral levofloxacin","volume":"99","author":"Jaruratanasirikul S.","year":"2018","journal-title":"Journal of the Medical Association of Thailand"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.6.1341"},{"issue":"6","key":"e_1_2_7_13_1","first-page":"605","article-title":"Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis","volume":"10","author":"Johnson J. 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