{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T02:14:09Z","timestamp":1782440049052,"version":"3.54.5"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lefamulin is being evaluated as a treatment for bacterial exacerbations in cystic fibrosis (CF). Ivacaftor is approved for the treatment of patients with CF. Lefamulin is a moderate CYP3A inhibitor and co\u2010administration with ivacaftor may result in a drug\u2013drug interaction (DDI). A CF population was built based on literature using the Simcyp Simulator. A previously developed and validated physiologically\u2010based pharmacokinetic (PBPK) model for ivacaftor was used. A PBPK model for lefamulin was developed and verified. Predicted concentrations and pharmacokinetic (PK) parameters for both ivacaftor and lefamulin in healthy subjects and patients with CF were in reasonable agreement with observed data (within 1.4\u2010fold, majority within 1.25\u2010fold). The lefamulin model as a CYP3A4 perpetrator was validated using a different Ki value for oral (p.o.) and intravenous (i.v.) routes. The simulated changes in area under the curve of ivacaftor in patients with CF when co\u2010administered with p.o. and i.v. lefamulin were weak\u2010to\u2010moderate. The predicted change in ivacaftor PK when co\u2010administered with oral lefamulin was less than observed between ivacaftor and fluconazole. These results suggest a low liability for a DDI between lefamulin and ivacaftor in patients with CF.<\/jats:p>","DOI":"10.1002\/psp4.13103","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T06:48:49Z","timestamp":1706856529000},"page":"589-598","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Physiologically\u2010based pharmacokinetic modeling of the <scp>drug\u2013drug<\/scp> interaction between ivacaftor and lefamulin in cystic fibrosis patients"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9997-7825","authenticated-orcid":false,"given":"Magali","family":"Amiel","sequence":"first","affiliation":[{"name":"Certara UK Ltd.  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3122-7120","authenticated-orcid":false,"given":"Alice","family":"Ke","sequence":"additional","affiliation":[{"name":"Certara UK Ltd.  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P.","family":"Gelone","sequence":"additional","affiliation":[{"name":"Nabriva Therapeutics US, Inc.  Fort Washington Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah M.","family":"Jones","sequence":"additional","affiliation":[{"name":"Certara UK Ltd.  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4863-7559","authenticated-orcid":false,"given":"Wolfgang","family":"Wicha","sequence":"additional","affiliation":[{"name":"Nabriva Therapeutics GmbH  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-017-1193-9"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.15155"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/69.3.531"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00932-9"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/67.5.912"},{"key":"e_1_2_9_7_1","unstructured":"FDA.Clinical pharmacology and biopharmaceutic review Kalydeco (ivacaftor).2012. Application Number: 203188Orig1s000. Accessed November 12 2023.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2012\/203188Orig1s000ClinPharmR.pdf"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s41030-020-00124-7"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008319707"},{"key":"e_1_2_9_10_1","unstructured":"\u00a92021 Cystic Fibrosis Foundation.Cystic Fibrosis Foundation Patient Registry 2020 Annual Data Report Bethesda Maryland. Accessed November 12 2023.https:\/\/www.cff.org\/sites\/default\/files\/2021\u201010\/2019\u2010Patient\u2010Registry\u2010Annual\u2010Data\u2010Report.pdf"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67353-3"},{"key":"e_1_2_9_12_1","unstructured":"FDA.NDA\/BLA multi\u2010disciplinary review and evaluation Xenleta (Lefamulin).2019. Application Number: 211672Orig1s000 211673Orig1s000. Accessed November 12 2023.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2019\/211672Orig1s000 %20211673Orig1s000MultidisciplineR.pdf"},{"key":"e_1_2_9_13_1","unstructured":"EMA.Summary of Product Characteristics Kalydeco (Ivacaftor). Accessed November 12 2023.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/kalydeco\u2010epar\u2010product\u2010information_en.pdf"},{"key":"e_1_2_9_14_1","unstructured":"FDA.Clinical pharmacology and biopharmaceutic review Symdeko (Tezacaftor\/ivacaftor);2017. Application Number: 210491Orig1s000. Accessed November 12 2023.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2018\/210491Orig1s000ClinPharmR.pdf"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12610"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-009-9099-y"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2009.12.002"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20502"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2022.11.008"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-014-0188-4"},{"key":"e_1_2_9_21_1","unstructured":"FDA.Drug development and drug interactions \u2013 Table of substrates inhibitors and inducers. Accessed February 2 2023.https:\/\/www.fda.gov\/drugs\/drug\u2010interactions\u2010labeling\/drug\u2010development\u2010and\u2010drug\u2010interactions\u2010table\u2010substrates\u2010inhibitors\u2010and\u2010inducers"},{"key":"e_1_2_9_22_1","unstructured":"DrugBank Online Website.Ivacaftor page. Accessed November 12 2023.https:\/\/go.drugbank.com\/drugs\/DB08820"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.13103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T05:42:06Z","timestamp":1712986926000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.13103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/psp4.13103"],"URL":"https:\/\/doi.org\/10.1002\/psp4.13103","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2]]},"assertion":[{"value":"2023-09-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}