{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:42:59Z","timestamp":1791434579488,"version":"4.3.3"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:00:00Z","timestamp":1630540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012399","name":"Biomedical Advanced Research and Development Authority","doi-asserted-by":"publisher","award":["HHSO100201300011C"],"award-info":[{"award-number":["HHSO100201300011C"]}],"id":[{"id":"10.13039\/100012399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To develop physiologically based pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) models to predict effective doses of gepotidacin in paediatrics for the treatment of pneumonic plague (<jats:italic>Yersinia pestis<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A gepotidacin PBPK model was constructed using a population\u2010based absorption, distribution, metabolism and excretion simulator, Simcyp\u00ae, with physicochemical and in vitro data, optimized with clinical data from a dose\u2010escalation intravenous (IV) study and a human mass balance study. A PopPK model was developed with pooled PK data from phase 1 studies with IV gepotidacin in healthy adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>For both the PopPK and PBPK models, body weight was found to be a key covariate affecting gepotidacin clearance. With PBPK, ~90% of the predicted PK for paediatrics fell between the 5th and 95th percentiles of adult values except for subjects weighing \u22645\u00a0kg. PopPK\u2010simulated paediatric means for <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> and AUC<jats:sub>(0\u2010\u03c4)<\/jats:sub> were similar to adult exposures across various weight brackets. The proposed dosing regimens were weight\u2010based for subjects \u226440\u2009kg and fixed\u2010dose for subjects &gt;40\u2009kg. Comparison of observed and predicted exposures in adults indicated that both PBPK and PopPK models achieved similar AUC and <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> for a given dose, but the <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> predictions with PopPK were slightly higher than with PBPK. The two models differed on dose predictions in children &lt;3\u00a0months old. The PopPK model may be suboptimal for low age groups due to the absence of maturation characterization of drug\u2010metabolizing enzymes involved with clearance in adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Both PBPK and PopPK approaches can reasonably predict gepotidacin exposures in children.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14996","type":"journal-article","created":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T17:52:24Z","timestamp":1626889944000},"page":"416-428","source":"Crossref","is-referenced-by-count":12,"title":["Comparison between physiologically based pharmacokinetic and population pharmacokinetic modelling to select paediatric doses of gepotidacin in plague"],"prefix":"10.1111","volume":"88","author":[{"given":"Dung","family":"Nguyen","sequence":"first","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jafar Sadik","family":"Shaik","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoying","family":"Tai","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Tiffany","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Perry","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Dumont","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gardiner","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Barth","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra","family":"Singh","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Hossain","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,2]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"World Health Organization.Antibiotic Resistance. 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