{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T08:04:18Z","timestamp":1758873858151,"version":"3.40.5"},"reference-count":16,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Glucocorticoids are 1 of the primary treatments in paediatric kidney transplantation. The aims of this study were: (i) to build a population pharmacokinetics (PPK) model of free prednisolone, which is the active form of prednisone, in paediatric kidney transplant recipients; (ii) to identify covariates accounting for interindividual variability (IIV) of pharmacokinetics (PK) parameters; and (iii) to investigate drug exposure\u2013safety relationships.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ninety\u2010seven samples were obtained from 39 paediatric kidney transplant recipients (aged 3.4\u201317.2\u00a0years) in order to investigate prednisone PPK. We selected children receiving oral prednisone as part of their immunosuppressive regimen. A PPK analysis was performed using Monolix.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 1\u2010compartment model best described prednisolone concentrations. Large IIV was observed as prednisolone was undetectable at H12 in some patients but could still be detected at H24 in others. Both bodyweight and ciclosporin cotreatment influenced the PK. The clearance (<jats:italic>CL<\/jats:italic><jats:sub>U<\/jats:sub>) and volume of distribution of free prednisolone allometrically scaled to 70\u2009kg were 27.6\u00a0L\/h and 101\u2009L. Ciclosporin cotreatment decreased <jats:italic>CL<\/jats:italic><jats:sub>U<\/jats:sub> by 67%. High blood pressure and new onset diabetes after transplantation were associated with daily free prednisolone exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study is the first analysis of prednisolone PPK in kidney\u2010transplanted children. Some of the IIV in the PK parameters was explained by bodyweight and ciclosporin cotreatment. These data suggest that dose adjustment is required after identifying variability factors to optimize efficacy and limit side effects. The use of therapeutic drug monitoring in kidney\u2010transplanted children may be useful, especially with respect to safety issues.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15610","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T10:18:48Z","timestamp":1669112328000},"page":"1532-1540","source":"Crossref","is-referenced-by-count":2,"title":["Prednisolone pharmacokinetics after oral prednisone administration in paediatric patients with kidney transplant"],"prefix":"10.1111","volume":"89","author":[{"given":"Camille","family":"de Truchis","sequence":"first","affiliation":[{"name":"Service de N\u00e9phrologie P\u00e9diatrique CRMR MARHEA, H\u00f4pital Necker Enfants Malades, Assistance Publique\u2013H\u00f4pitaux de Paris (AP\u2013HP)  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na\u00efm","family":"Bouazza","sequence":"additional","affiliation":[{"name":"EA 7323, Universit\u00e9 Paris Cit\u00e9, Pharmacologie et \u00e9valuations th\u00e9rapeutiques chez l'enfant et la femme enceinte  Paris France"},{"name":"Unit\u00e9 de Recherche Clinique Universit\u00e9 de Paris Necker\/Cochin, H\u00f4pital Tarnier  Paris France"},{"name":"CIC\u20101419 Inserm, Cochin\u2010Necker  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9928-3404","authenticated-orcid":false,"given":"Frantz","family":"Foissac","sequence":"additional","affiliation":[{"name":"EA 7323, Universit\u00e9 Paris Cit\u00e9, Pharmacologie et \u00e9valuations th\u00e9rapeutiques chez l'enfant et la femme enceinte  Paris France"},{"name":"Unit\u00e9 de Recherche Clinique Universit\u00e9 de Paris Necker\/Cochin, H\u00f4pital Tarnier  Paris France"},{"name":"CIC\u20101419 Inserm, Cochin\u2010Necker  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Charbit","sequence":"additional","affiliation":[{"name":"Service de N\u00e9phrologie P\u00e9diatrique CRMR MARHEA, H\u00f4pital Necker Enfants Malades, Assistance Publique\u2013H\u00f4pitaux de Paris (AP\u2013HP)  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laur\u00e8ne","family":"Dehoux","sequence":"additional","affiliation":[{"name":"Service de N\u00e9phrologie P\u00e9diatrique CRMR MARHEA, H\u00f4pital Necker Enfants Malades, Assistance Publique\u2013H\u00f4pitaux de Paris (AP\u2013HP)  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabrielle","family":"Lui","sequence":"additional","affiliation":[{"name":"EA 7323, Universit\u00e9 Paris Cit\u00e9, Pharmacologie et \u00e9valuations th\u00e9rapeutiques chez l'enfant et la femme enceinte  Paris France"},{"name":"CIC\u20101419 Inserm, Cochin\u2010Necker  Paris France"},{"name":"Service de Pharmacologie Clinique H\u00f4pital Cochin, AP\u2010HP, Groupe Hospitalier Paris Centre  Paris 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