{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:47:15Z","timestamp":1791362835297,"version":"4.3.1"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12]]},"abstract":"\n Background:<\/jats:title>\n Mycophenolate mofetil (MMF) plays an increasingly important role in the treatment of children with nephrotic syndrome, especially in steroid sparing protocols. Recent publications show the relationship of exposure to its active moiety mycophenolic acid (MPA) and clinical efficacy. Performance of full-time pharmacokinetic (PK) profiles, however, is inconvenient and laborious. Established limited sampling strategies (LSS) to estimate the area under the concentration (AUC) versus time curve of MPA (MPA-AUC) in pediatric renal transplant recipients cannot be easily transferred to children suffering from nephrotic syndrome, mainly because of the lack of concomitant immunosuppressive therapy. We therefore aimed for the generation and validation of a LSS to estimate MPA exposure to facilitate therapeutic drug monitoring in children with nephrotic syndrome.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n We performed 27 complete PK profiles in 23 children in remission [mean age (\u00b1SD):12.3 \u00b1 4.26 years] to generate and validate an LSS. Sampling time points were before administration (C\n 0<\/jats:sub>\n ) and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours after the administration of MMF. MPA was measured by enzyme multiplied immunoassay technique. There was no concomitant treatment with calcineurin inhibitors.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Mean daily dose of MMF was 927 \u00b1 209 mg\/m\n 2<\/jats:sup>\n of body surface area resulting in a mean MPA-AUC\n 0-12<\/jats:sub>\n value of 59.2 \u00b1 29.3 mg \u00d7 h\/L and a predose level of 3.03 \u00b1 2.24 mg\/L. Between-patient variability of dose-normalized MPA-AUC\n 0-12<\/jats:sub>\n was high (coefficient of variation: 45.5%). Correlation of predose levels with the corresponding MPA-AUC\n 0-12<\/jats:sub>\n was moderate (\n r<\/jats:italic>\n 2<\/jats:sup>\n = 0.59) in a subgroup of 18 patients (20 PK profiles, generation group). An algorithm based on 3 PK sampling time points during the first 2 hours after MMF dosing (estimated AUC\n 0-12<\/jats:sub>\n = 8.7 + 4.63 \u00d7 C\n 0<\/jats:sub>\n + 1.90 \u00d7 C\n 1<\/jats:sub>\n + 1.52 \u00d7 C\n 2<\/jats:sub>\n ) was able to predict MPA-AUC with a low percentage prediction error (3.88%) and a good correlation of determination (\n r<\/jats:italic>\n 2<\/jats:sup>\n = 0.90). Validation of this algorithm in a randomized separate group of 6 patients (7 PK profiles, validation group) resulted in comparably good correlation (\n r<\/jats:italic>\n 2<\/jats:sup>\n = 0.95) and low percentage prediction error (5.57%).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n An abbreviated profile within the first 2 hours after MMF dosing gives a good estimate of MPA exposure in children with nephrotic syndrome and hence has the potential to optimize MMF therapy.<\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/ftd.0000000000000671","type":"journal-article","created":{"date-parts":[[2019,8,17]],"date-time":"2019-08-17T03:46:49Z","timestamp":1566013609000},"page":"696-702","source":"Crossref","is-referenced-by-count":23,"title":["Generation and Validation of a Limited Sampling Strategy to Monitor Mycophenolic Acid Exposure in Children With Nephrotic Syndrome"],"prefix":"10.1097","volume":"41","author":[{"given":"Marcus R.","family":"Benz","sequence":"first","affiliation":[{"name":"Pediatric Nephrology, Children's and Adolescents' Hospital, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasmus","family":"Ehren","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Children's and Adolescents' Hospital, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Kleinert","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Children's Hospital, Memmingen;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Drug Monitoring, Faculty of Medicine and University Hospital Cologne, Cologne;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutta","family":"Gellermann","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Charit\u00e9 Universit\u00e4tsmedizin Berlin CVdK, Berlin; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Fehrenbach","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Children's Hospital, Memmingen;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, Dr. von Haunersches Kinderspital, University Children's Hospital, LMU, Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz T.","family":"Weber","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Children's and Adolescents' Hospital, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20230814","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/BF01956754","article-title":"Long versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children","volume":"152","author":"Ehrich","year":"1993","journal-title":"Eur J Pediatr."},{"key":"R2-20230814","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1542\/peds.2008-1559","article-title":"Management of childhood onset nephrotic syndrome","volume":"124","author":"Gipson","year":"2009","journal-title":"Pediatrics."},{"key":"R3-20230814","first-page":"CD002290","article-title":"Non-corticosteroid treatment for nephrotic syndrome in children","volume":"23","author":"Hodson","year":"2008","journal-title":"Cochrane Database Syst Rev."},{"key":"R4-20230814","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1681\/ASN.V85769","article-title":"Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children","volume":"8","author":"Tarshish","year":"1997","journal-title":"J Am Soc Nephrol."},{"key":"R5-20230814","first-page":"380","article-title":"Short versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children","volume":"1","year":"1988","journal-title":"Lancet."},{"key":"R6-20230814","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1007\/s00467-007-0617-9","article-title":"Treatment with mycophenolate mofetil and prednisolone for steroid-dependent nephrotic syndrome","volume":"22","author":"Afzal","year":"2007","journal-title":"Pediatr Nephrol."},{"key":"R7-20230814","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1053\/j.ajkd.2003.08.011","article-title":"Mycophenolate mofetil and prednisolone therapy in children with steroid-dependent nephrotic 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mycophenolic acid (MPA) and determinants of MPA free fraction in pediatric and adult renal transplant recipients. German Study group on Mycophenolate Mofetil Therapy in Pediatric Renal Transplant Recipients","volume":"9","author":"Weber","year":"1998","journal-title":"J Am Soc Nephrol."},{"key":"R18-20230814","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1093\/clinchem\/48.3.517","article-title":"Comparison of the Emit immunoassay with HPLC for therapeutic drug monitoring of mycophenolic acid in pediatric renal-transplant recipients on mycophenolate mofetil therapy","volume":"48","author":"Weber","year":"2002","journal-title":"Clin Chem."},{"key":"R19-20230814","doi-asserted-by":"crossref","first-page":"341","DOI":"10.2215\/CJN.07111009","article-title":"Transplantation Society Consensus Group on TDMoMPA Consensus report on therapeutic drug monitoring of mycophenolic acid in solid organ transplantation","volume":"5","author":"Kuypers","year":"2010","journal-title":"Clin J Am Soc 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Monit."},{"key":"R29-20230814","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.phrs.2011.01.009","article-title":"Development of a Bayesian estimator for the therapeutic drug monitoring of mycophenolate mofetil in children with idiopathic nephrotic syndrome","volume":"63","author":"Saint-Marcoux","year":"2011","journal-title":"Pharmacol Res."},{"key":"R30-20230814","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1007\/s00228-011-1203-4","article-title":"Inosine monophosphate dehydrogenase activity in paediatrics: age-related regulation and response to mycophenolic acid","volume":"68","author":"Rother","year":"2012","journal-title":"Eur J Clin Pharmacol."},{"key":"R31-20230814","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1542\/peds.58.2.259","article-title":"A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine","volume":"58","author":"Schwartz","year":"1976","journal-title":"Pediatrics."}],"container-title":["Therapeutic Drug Monitoring"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/FTD.0000000000000671","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T18:14:21Z","timestamp":1692036861000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/FTD.0000000000000671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019]]}},"URL":"https:\/\/doi.org\/10.1097\/ftd.0000000000000671","relation":{},"ISSN":["0163-4356"],"issn-type":[{"value":"0163-4356","type":"print"}],"subject":[],"published":{"date-parts":[[2019,12]]}}}