{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T14:54:25Z","timestamp":1770994465876,"version":"3.50.1"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Missed doses of mycophenolate mofetil (MMF) are frequent in transplant recipients and may lead to subtherapeutic exposure to mycophenolic acid (MPA), potentially compromising graft function. However, current guidance on how to manage such deviations remains empirical and is not supported by pharmacokinetic evidence.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We used two validated population pharmacokinetic models of MPA to simulate steady-state exposure in virtual cohorts of renal transplant recipients treated with MMF. Scenarios included full missed doses, delays in intake (2\u201310 hours), and compensation strategies (50% or 100% added at the next dose). Simulations were performed for six dose regimens (500\u20131250\u2009mg BID) and analyzed in terms of AUC<jats:sub>0\u201312h<\/jats:sub>, proportion of patients outside the target range (30\u201360 mg\u00b7h\/L), and time to return to steady state.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>A fully missed dose resulted in a 40\u201360% reduction in AUC<jats:sub>0\u201312h<\/jats:sub>, with delayed return to steady state (up to 72 hours). Delays \u22646 hours caused minimal impact (&lt;15% reduction). Full-dose compensation frequently overshot the therapeutic window, especially in higher-dose regimens. In contrast, adding 50% of the missed dose restored exposure safely and rapidly. When exact compensation was not feasible, rounding down to the nearest available formulation minimized overexposure.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Model-based simulations suggest that a rational response to MMF dose omissions can mitigate underexposure while avoiding toxicity. These strategies may support clinicians in managing missed doses and optimizing immunosuppressive therapy in kidney transplant recipients.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0330854","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T17:25:07Z","timestamp":1756401907000},"page":"e0330854","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Population pharmacokinetic modeling of missed mycophenolate mofetil doses: Impact on exposure and exploration of mitigation strategies"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5103-0827","authenticated-orcid":true,"given":"Franck","family":"Maizaud","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selim","family":"Arraki-Zava","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamza","family":"Sayadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3356-557X","authenticated-orcid":true,"given":"Yeleen","family":"Fromage","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Marquet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1695-0695","authenticated-orcid":true,"given":"Jean-Baptiste","family":"Woillard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9637-5813","authenticated-orcid":true,"given":"Caroline","family":"Monchaud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"issue":"2","key":"pone.0330854.ref001","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1097\/FTD.0000000000000871","article-title":"Personalized Therapy for Mycophenolate: Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology","volume":"43","author":"S Bergan","year":"2021","journal-title":"Ther Drug Monit"},{"issue":"11","key":"pone.0330854.ref002","doi-asserted-by":"crossref","first-page":"2496","DOI":"10.1111\/j.1600-6143.2007.01983.x","article-title":"Individualized mycophenolate mofetil dosing based on drug exposure significantly improves patient outcomes after renal transplantation","volume":"7","author":"Y Le Meur","year":"2007","journal-title":"Am J Transplant"},{"issue":"2","key":"pone.0330854.ref003","doi-asserted-by":"crossref","first-page":"341","DOI":"10.2215\/CJN.07111009","article-title":"Consensus report on therapeutic drug monitoring of mycophenolic acid in solid organ transplantation","volume":"5","author":"DRJ Kuypers","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"issue":"12","key":"pone.0330854.ref004","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.2337\/dci22-0027","article-title":"Diabetes Management in Chronic Kidney Disease: A Consensus Report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO","volume":"45","author":"IH de Boer","year":"2022","journal-title":"). 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