{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T16:12:37Z","timestamp":1778083957899,"version":"3.51.4"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Maribavir is currently administered at a dose of 400\u2005mg twice daily (q12h) for the treatment of cytomegalovirus (CMV) infections in transplant recipients. However, virological failure rates of up to 40% have been reported in clinical practice, with potentially severe consequences and the selection of mutant strains.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aims to evaluate, in silico, the pharmacokinetic (PK) and pharmacodynamic (PD) interest of alternative maribavir dosing regimens using population pharmacokinetic (POPPK) modelling and Monte Carlo simulations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A published two-compartment POPPK model with first-order absorption and an absorption lag time was implemented. Monte Carlo simulations (n\u200a=\u200a10\u200a000 virtual PK profiles) were performed for maribavir regimens of 400, 600, and 800\u2005mg administered q12h and every 8\u2005h (q8h). PK metrics, including trough concentration (C0) and area under the concentration\u2013time curve (AUC), as well as probability of target attainment (PTA), were compared across regimens at steady state.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The standard 400\u2005mg q12h regimen resulted in the lowest PTA, falling below 90% for a pharmacologically active inhibitory concentration 50 of 2\u2005mg\/L. In contrast, q8h regimens substantially improved PTA across targets and were associated with reduced interindividual variability in C0.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Increasing dosing frequency to a three-times-daily regimen improved PK\/PD target attainment compared with the standard q12h regimen. These findings support the need for prospective clinical and pharmacoeconomic studies to assess the benefit\u2013risk balance of alternative maribavir dosing strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag153","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:32:01Z","timestamp":1776771121000},"source":"Crossref","is-referenced-by-count":0,"title":["Monte Carlo simulations identify suboptimal PK\/PD target attainment with standard maribavir dosing"],"prefix":"10.1093","volume":"81","author":[{"given":"Yeleen","family":"Fromage","sequence":"first","affiliation":[{"name":"Inserm CIC 1435, CHU Dupuytren , Limoges ,","place":["France"]},{"name":"Inserm UMR1248, Pharmacology & Transplantation, University of Limoges , Limoges ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamza","family":"Sayadi","sequence":"additional","affiliation":[{"name":"Inserm UMR1248, Pharmacology & Transplantation, University of Limoges , Limoges ,","place":["France"]},{"name":"Department of Pharmacology, Toxicology and Pharmacovigilance, CHU Limoges , Limoges ,","place":["France"]},{"name":"University Hospital Federation Survival Optimization in Organ Transplantation (FHU SUPORT) , Limoges ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Labriffe","sequence":"additional","affiliation":[{"name":"Inserm UMR1248, Pharmacology & Transplantation, University of Limoges , Limoges ,","place":["France"]},{"name":"Department of Pharmacology, Toxicology and Pharmacovigilance, CHU Limoges , Limoges ,","place":["France"]},{"name":"University Hospital Federation Survival Optimization in Organ Transplantation (FHU SUPORT) , Limoges ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyrielle","family":"Codde","sequence":"additional","affiliation":[{"name":"Inserm UMR1248, Pharmacology & Transplantation, University of Limoges , Limoges ,","place":["France"]},{"name":"Infectious and Tropical Diseases Unit, CHU Dupuytren , Limoges ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9787-1421","authenticated-orcid":false,"given":"Sophie","family":"Alain","sequence":"additional","affiliation":[{"name":"University Hospital Federation Survival Optimization in Organ Transplantation (FHU SUPORT) , Limoges ,","place":["France"]},{"name":"Microbiology Department, CHU Limoges , Limoges ,","place":["France"]},{"name":"RESINFIT, UMR1092, Inserm, University of Limoges, CHU Limoges , Limoges ,","place":["France"]},{"name":"National Reference Center for Herpesviruses, CHU Limoges , Limoges ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Marquet","sequence":"additional","affiliation":[{"name":"Inserm UMR1248, Pharmacology & Transplantation, University of Limoges , Limoges ,","place":["France"]},{"name":"Department of Pharmacology, Toxicology and Pharmacovigilance, CHU Limoges , Limoges ,","place":["France"]},{"name":"University Hospital Federation Survival Optimization in Organ Transplantation (FHU SUPORT) , Limoges ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1695-0695","authenticated-orcid":false,"given":"Jean-Baptiste","family":"Woillard","sequence":"additional","affiliation":[{"name":"Inserm CIC 1435, CHU Dupuytren , Limoges ,","place":["France"]},{"name":"Inserm UMR1248, Pharmacology & Transplantation, University of Limoges , Limoges ,","place":["France"]},{"name":"Department of Pharmacology, Toxicology and Pharmacovigilance, CHU Limoges , Limoges ,","place":["France"]},{"name":"University Hospital Federation Survival Optimization in Organ Transplantation (FHU SUPORT) , Limoges ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9637-5813","authenticated-orcid":false,"given":"Caroline","family":"Monchaud","sequence":"additional","affiliation":[{"name":"Inserm UMR1248, Pharmacology & Transplantation, University of Limoges , Limoges ,","place":["France"]},{"name":"Department of Pharmacology, Toxicology and Pharmacovigilance, CHU Limoges , Limoges ,","place":["France"]},{"name":"University Hospital Federation Survival Optimization in Organ Transplantation (FHU SUPORT) , Limoges ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"2026050611245095500_dkag153-B1","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1097\/TP.0000000000005374","article-title":"The fourth international consensus guidelines on the management of cytomegalovirus in solid organ transplantation","volume":"109","author":"Kotton","year":"2025","journal-title":"Transplantation"},{"key":"2026050611245095500_dkag153-B2","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1002\/rmv.615","article-title":"Function of human cytomegalovirus UL97 kinase in viral infection and its inhibition by maribavir","volume":"19","author":"Prichard","year":"2009","journal-title":"Rev Med Virol"},{"key":"2026050611245095500_dkag153-B3","author":"Anon"},{"key":"2026050611245095500_dkag153-B4","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1007\/s10928-024-09939-2","article-title":"Population pharmacokinetics and exposure-response relationships of maribavir in transplant recipients with cytomegalovirus infection","volume":"51","author":"Song","year":"2024","journal-title":"J Pharmacokinet Pharmacodyn"},{"key":"2026050611245095500_dkag153-B5","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1056\/NEJMoa1714656","article-title":"Maribavir for preemptive treatment of cytomegalovirus reactivation","volume":"381","author":"Maertens","year":"2019","journal-title":"N Engl J Med"},{"key":"2026050611245095500_dkag153-B6","doi-asserted-by":"publisher","first-page":"e0321180","DOI":"10.1371\/journal.pone.0321180","article-title":"Optimizing CMV therapy: population pharmacokinetics and Monte Carlo simulations for letermovir and maribavir dosage","volume":"20","author":"Fromage","year":"2025","journal-title":"PLoS One"},{"key":"2026050611245095500_dkag153-B7","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1093\/cid\/ciad709","article-title":"Treatment for first cytomegalovirus infection post\u2013hematopoietic cell transplant in the AURORA trial: a multicenter, double-blind, randomized, phase 3 trial comparing maribavir with valganciclovir","volume":"78","author":"Papanicolaou","year":"2024","journal-title":"Clin Infect Dis"},{"key":"2026050611245095500_dkag153-B8","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1002\/psp4.70054","article-title":"Population pharmacokinetics and exposure-response relationships of maribavir in transplant recipients with first episode or refractory cytomegalovirus","volume":"14","author":"Sun","year":"2025","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"key":"2026050611245095500_dkag153-B9","author":"Takeda"},{"key":"2026050611245095500_dkag153-B10","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1002\/cpdd.1247","article-title":"Pharmacokinetics and safety evaluation of maribavir in healthy Japanese and matched white participants: a phase 1, open-label study","volume":"12","author":"Song","year":"2023","journal-title":"Clin Pharm Drug Dev"},{"key":"2026050611245095500_dkag153-B11","author":"Shire"},{"key":"2026050611245095500_dkag153-B12","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1002\/psp4.12943","article-title":"Population pharmacokinetic modeling and simulation of maribavir to support dose selection and regulatory approval in adolescents with posttransplant refractory cytomegalovirus","volume":"12","author":"Sun","year":"2023","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"key":"2026050611245095500_dkag153-B13","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1002\/psp4.12467","article-title":"Quantitative systems pharmacology and physiologically-based pharmacokinetic modeling with mrgsolve: a hands-on tutorial","volume":"8","author":"Elmokadem","year":"2019","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"key":"2026050611245095500_dkag153-B14","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.3390\/jcm8091382","article-title":"Chronic use of proton-pump inhibitors and iron status in renal transplant recipients","volume":"8","author":"Douwes","year":"2019","journal-title":"J Clin Med"},{"key":"2026050611245095500_dkag153-B15","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.1111\/tri.14110","article-title":"Type of proton-pump inhibitor and risk of iron deficiency in kidney transplant recipients\u2014results from the TransplantLines Biobank and Cohort Study","volume":"34","author":"Douwes","year":"2021","journal-title":"Transpl Int"},{"key":"2026050611245095500_dkag153-B16","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1093\/cid\/ciy706","article-title":"Maribavir for refractory or resistant cytomegalovirus infections in hematopoietic-cell or solid-organ transplant recipients: a randomized, dose-ranging, double-blind, phase 2 study","volume":"68","author":"Papanicolaou","year":"2019","journal-title":"Clin Infect Dis"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/6\/dkag153\/68229974\/dkag153.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/6\/dkag153\/68229974\/dkag153.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T15:24:56Z","timestamp":1778081096000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/doi\/10.1093\/jac\/dkag153\/8671048"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":16,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,5,5]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkag153","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,6]]},"published":{"date-parts":[[2026,5,5]]},"article-number":"dkag153"}}