{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:21:26Z","timestamp":1788402086076,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002997","name":"Nierstichting","doi-asserted-by":"publisher","award":["CP16.03"],"award-info":[{"award-number":["CP16.03"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Prednisolone is the cornerstone of treatment for idiopathic nephrotic syndrome in children, but is associated with marked side\u2010effects. Therapeutic drug monitoring using saliva would be a patient\u2010friendly option to monitor prednisolone treatment. To assess the feasibility of saliva monitoring, we described the pharmacokinetics (PK) of unbound prednisolone in plasma and saliva of children with first onset steroid\u2010sensitive nephrotic syndrome (SSNS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Children (age 2\u201316\u2009years) with SSNS participating in a randomized, placebo\u2010controlled trial with levamisole were treated with an 18\u2010week tapering schedule of prednisolone. Five serial samples were collected at 4 (saliva) and 8\u00a0weeks (saliva and plasma) after first onset. A nonlinear mixed\u2010effects model was used to estimate the PK parameters of unbound prednisolone and the saliva\u2010to\u2010plasma ratio. Monte Carlo simulations were performed to assess the predictive performance of saliva monitoring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From 39 children, 109 plasma and 275 saliva samples were available. Estimates (relative squared error) of unbound plasma clearance and volume of distribution were 93 (5%) L\u2009h<jats:sup>\u22121<\/jats:sup> 70\u2009kg<jats:sup>\u22121<\/jats:sup> and 158 (7%) L 70\u2009kg<jats:sup>\u22121<\/jats:sup>, respectively. Typical saliva\u2010to\u2010plasma ratio was 1.30 (8%). Monte Carlo simulations demonstrated that on basis of 4 saliva samples and a single plasma sample unbound plasma area\u2010under\u2010the\u2010concentration\u2013time curve can be predicted within 20% imprecision in 79% of the patients compared to 87% based on 4 plasma samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Saliva proved to be a reliable and patient\u2010friendly option to determine prednisolone plasma exposure in children with SSNS. This opens opportunities for further PK and pharmacodynamics studies of prednisolone in a variety of paediatric conditions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16066","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:34:22Z","timestamp":1712795662000},"page":"1677-1687","source":"Crossref","is-referenced-by-count":2,"title":["Saliva monitoring of prednisolone in children with first onset steroid\u2010sensitive nephrotic syndrome: Is it possible?"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6386-5154","authenticated-orcid":false,"given":"Floor","family":"Veltkamp","sequence":"first","affiliation":[{"name":"Department of Pediatric Nephrology, Emma Children's Hospital Amsterdam University Medical Centers, location University of Amsterdam  Amsterdam The Netherlands"},{"name":"Amsterdam Reproduction &amp; Development  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel C. M.","family":"Pistorius","sequence":"additional","affiliation":[{"name":"Department of Pharmacy &amp; Clinical Pharmacology Amsterdam University Medical Centers, location University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elske M.","family":"Mak\u2010Nienhuis","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Emma Children's Hospital Amsterdam University Medical Centers, location University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel F.","family":"Schreuder","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Amalia Children's Hospital Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia H. M.","family":"Bouts","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Emma Children's Hospital Amsterdam University Medical Centers, location University of Amsterdam  Amsterdam The Netherlands"},{"name":"Amsterdam Reproduction &amp; Development  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron A. A.","family":"Math\u00f4t","sequence":"additional","affiliation":[{"name":"Department of Pharmacy &amp; Clinical Pharmacology Amsterdam University Medical Centers, location University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"LEARNS consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(18)30536\u20101"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2021.05.021"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V85769"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467\u2010021\u201005135\u20103"},{"issue":"3","key":"e_1_2_11_6_1","first-page":"150","article-title":"Syndrome n\u00e9phrotique pur (ou n\u00e9phrose) corticosensible de l'enfant: Protocole de traitement propos\u00e9 par la Soci\u00e9t\u00e9 de N\u00e9phrologie P\u00e9diatrique","volume":"1","author":"B\u00e9rard \u00c9","year":"2005","journal-title":"Nephrologie et Therapeutique"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.15035"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e3282f51031"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u20104731(84)90288\u20107"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000045"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20102952(82)90172\u20101"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010199019020\u201000003"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000308"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.65.2.196"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.1730"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen\u20102018\u2010027011"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008030287"},{"key":"e_1_2_11_18_1","unstructured":"R Core Team.R: a language and environment for statistical computing. 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