{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:28:07Z","timestamp":1772774887594,"version":"3.50.1"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Shanghai Municipal Health Commission Clinical Research Youth Project","award":["20224Y0121"],"award-info":[{"award-number":["20224Y0121"]}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82204544"],"award-info":[{"award-number":["82204544"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fudan University Scientific Research Foundation for Talented Scholars","award":["JIF301052"],"award-info":[{"award-number":["JIF301052"]}]},{"name":"NHMRC Investigator Grant","award":["GNT1194694"],"award-info":[{"award-number":["GNT1194694"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,10,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Intravenous ganciclovir (GCV) is used for the treatment of cytomegalovirus (CMV) infection in immunocompromised children. Although the therapeutic target for treatment is unclear, studies have shown a serum area under the concentration\u2013time curve (AUC\n              <jats:sub>24h<\/jats:sub>\n              ) \u226540 mg\/L\u00b7h correlates with effective CMV prevention. This study aimed to externally validate existing GCV population pharmacokinetic (PopPK) models and develop a model if needed and evaluate the serum AUC\n              <jats:sub>24h<\/jats:sub>\n              achieved with standard GCV dosing and propose an optimized dosing strategy for immunocompromised children. Ganciclovir drug monitoring data from two pediatric hospitals were retrospectively collected, and published pediatric PopPK models were externally validated. The population AUC\n              <jats:sub>24h<\/jats:sub>\n              with standard GCV dosing (5 mg\/kg twice daily) was calculated, and an optimized dosing strategy was determined using Monte Carlo simulations to achieve an AUC\n              <jats:sub>24h<\/jats:sub>\n              between 40 and 100 mg\/L\u00b7h. Overall, 161 samples from 23 children with a median (range) age of 9.0 years (0.4\u201317.0) and weight of 28.2 kg (5.6\u201373.3) were analyzed. Transferability of published pediatric PopPK models was limited. Thus, a one-compartment model with first-order absorption and elimination with weight and serum creatinine as covariates was developed. The median (5th\u201395th percentiles) steady state AUC\n              <jats:sub>24h<\/jats:sub>\n              with standard dosing was 38.3 mg\/L\u00b7h (24.8\u2013329.2) with 13 children having an AUC\n              <jats:sub>24h<\/jats:sub>\n              &lt;40 mg\/L\u00b7h, particularly those aged &lt;4 years (8\/13). An optimized simulated GCV dosing regimen, ranging from 2 to 13 mg\/kg twice daily for children with normal renal function, achieved 61%\u201378% probability of target attainment. Standard GCV dosing likely results in inadequate drug exposure in more than half of the children, particularly those aged &lt;4 years. An optimized dosing regimen has been proposed for clinical validation.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00525-24","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T13:00:25Z","timestamp":1726664425000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Serum ganciclovir drug exposure in children receiving standard ganciclovir dosing"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9057-4520","authenticated-orcid":false,"given":"Wenyu","family":"Yang","sequence":"first","affiliation":[{"name":"Minhang Hospital &amp; School of Pharmacy, Fudan University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Irwin","sequence":"additional","affiliation":[{"name":"Centre for Clinical Research, The University of Queensland, Brisbane, Queensland, Australia"},{"name":"Infection Management and Prevention Service, Queensland Children\u2019s Hospital, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Weerdenburg","sequence":"additional","affiliation":[{"name":"Children\u2019s Cancer Centre, Royal Children\u2019s Hospital, Melbourne, Victoria, Australia"},{"name":"Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Antimicrobial Group, Murdoch Children\u2019s Research Institute, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brett","family":"McWhinney","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Pathology Queensland, Royal Brisbane and Women\u2019s Hospital, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"Cole","sequence":"additional","affiliation":[{"name":"Department of Haematology, Royal Children\u2019s Hospital, Melbourne, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Royal Children\u2019s Hospital, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6623-3523","authenticated-orcid":false,"given":"Bing","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Minhang Hospital, Fudan University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3295-619X","authenticated-orcid":true,"given":"Xiao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Minhang Hospital &amp; School of Pharmacy, Fudan University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Gwee","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Antimicrobial Group, Murdoch Children\u2019s Research Institute, Victoria, Australia"},{"name":"Department of General Medicine, Royal Children\u2019s Hospital, Melbourne, Victoria, 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