{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:07:14Z","timestamp":1773011234367,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204544"],"award-info":[{"award-number":["82204544"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Ganciclovir (GCV) is commonly used to treat cytomegalovirus (CMV) infections in immunocompromised children. Currently, the therapeutic target for effective treatment is unclear: Adult studies suggest that a serum area under the concentration\u2010time curve (AUC\n                      <jats:sub>24h<\/jats:sub>\n                      ) \u226540 mg\/L\u00b7h correlates with effective CMV prevention. The aim of this study was to determine the serum GCV therapeutic target for the treatment of CMV viraemia in immunocompromised children.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data from a multicenter retrospective audit of GCV dosing, therapeutic drug monitoring and plasma CMV viral loads in immunocompromised children were analysed using piecewise linear regression to determine viral dynamics during GCV treatment periods. A published population pharmacokinetic model from the same cohort was used to derive post hoc average daily AUC\n                      <jats:sub>24h<\/jats:sub>\n                      . An E\n                      <jats:sub>max<\/jats:sub>\n                      model was developed in NONMEM to explore the effect of drug exposure on viral dynamics, adjusting for immune status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fourteen children with 185 viral loads were included, encompassing 30 periods of viral load increases and 28 periods of decline. The estimated natural viral replication rate was 0.237 log\n                      <jats:sub>10<\/jats:sub>\n                      copies\/mL\/day (doubling time 1.3\u00a0days). White cell count (WCC) significantly affected the viral decline rate, with a maximum GCV\u2010induced viral decline rate of 0.238 log\n                      <jats:sub>10<\/jats:sub>\n                      copies\/mL\/day. The GCV AUC\n                      <jats:sub>24h<\/jats:sub>\n                      corresponding to 90% maximal replication suppression and elimination effects were approximately 40 and 100\u2009mg\/L\u00b7h, respectively, when the WCC was 3.7\u2009\u00d7\u200910\n                      <jats:sup>9<\/jats:sup>\n                      \/L.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      A serum GCV AUC\n                      <jats:sub>24h<\/jats:sub>\n                      target of 40\u2013100\u2009mg\/L\u00b7h may serve as a preliminary reference for the treatment of CMV infection in immunocompromised children. Notably, the therapeutic target is affected by the individual's immune status.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70315","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T03:58:42Z","timestamp":1760414322000},"page":"851-859","source":"Crossref","is-referenced-by-count":1,"title":["Identifying a therapeutic target for ganciclovir against cytomegalovirus in immunocompromised children"],"prefix":"10.1002","volume":"92","author":[{"given":"Wenyu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, 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's Hospital  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Weerdenburg","sequence":"additional","affiliation":[{"name":"Children's Cancer Centre Royal Children's Hospital  Melbourne Victoria Australia"},{"name":"Department of Paediatrics The University of Melbourne  Melbourne Victoria Australia"},{"name":"Antimicrobial Group Murdoch Children's 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's Hospital  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"Cole","sequence":"additional","affiliation":[{"name":"Children's Cancer Centre Royal Children's Hospital  Melbourne Victoria Australia"},{"name":"Department of Paediatrics The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of General Medicine Royal Children's Hospital  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3295-619X","authenticated-orcid":false,"given":"Xiao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4016-8986","authenticated-orcid":false,"given":"Amanda","family":"Gwee","sequence":"additional","affiliation":[{"name":"Department of Paediatrics The University of Melbourne  Melbourne Victoria Australia"},{"name":"Antimicrobial Group Murdoch Children's Research Institute  Victoria Australia"},{"name":"Department of General Medicine Royal Children's Hospital  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/v6052038"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2016.1221022"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10010077"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000164512.99703.AD"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/petr.12030"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02254\u201020"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2431"},{"issue":"2023","key":"e_1_2_11_9_1","doi-asserted-by":"crossref","DOI":"10.1128\/aac.01550-22","article-title":"Population pharmacokinetics of ganciclovir in allogeneic hematopoietic stem cell transplant patients","volume":"67","author":"Selby PR","year":"2023","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkab419"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01665\u201022"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3277"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00525\u201024"},{"key":"e_1_2_11_14_1","unstructured":"Hoz\u00e9N.A multi\u2010scale modelling framework to assess the relationship between SARS\u2010CoV\u20102 viral load and transmission in household studies population approach group in Europe(PAGE) Rome Italy. 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