{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:58:39Z","timestamp":1785549519922,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010438","name":"Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu","doi-asserted-by":"publisher","award":["502-05-33064130-10156"],"award-info":[{"award-number":["502-05-33064130-10156"]}],"id":[{"id":"10.13039\/501100010438","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>In pediatric nephrotic syndrome, recommended mycophenolic acid (MPA) pharmacokinetics are higher than those for transplant recipients. In MPA therapeutic monitoring, inosine-5\u2032-monophosphate dehydrogenase (IMPDH) activity may be useful. We modified the method established for renal transplant recipients and determined IMPDH activity in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and children (4\u201316 years) with nephrotic syndrome treated with mycophenolate mofetil (MMF). From children, four blood samples were collected, and MPA concentrations were also determined. IMPDH activity was calculated using xanthosine monophosphate (XMP) normalized with adenosine monophosphate (AMP), both determined with the HPLC-UV method. The modified method was accurate, precise, and linear for AMP and XMP within 0.50\u201350.0 \u03bcmoL\/L. Mean IMPDH activity in volunteers was 45.97 \u00b1 6.24 \u00b5moL\u00b7s\u22121\u00b7moL\u22121 AMP, whereas for children, the values were variable and amounted to 39.23 \u00b1 27.40 \u00b5moL\u00b7s\u22121\u00b7moL\u22121 AMP and 17.97 \u00b1 15.24 \u00b5moL\u00b7s\u22121\u00b7moL\u22121 AMP before the next MMF dose and 1 h afterward, respectively. The modified method may be applied to IMPDH activity determination in children with nephrotic syndrome treated with MMF. IMPDH activity should be determined after one thawing of PBMCs due to the change in AMP and XMP concentrations after subsequent thawing. For children, the lowest IMPDH activity was observed concomitantly with the highest MPA concentration.<\/jats:p>","DOI":"10.3390\/ph13080200","type":"journal-article","created":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T11:15:27Z","timestamp":1597749327000},"page":"200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Application of Inosine 5\u2032-Monophosphate Dehydrogenase Activity Determination in Peripheral Blood Mononuclear Cells for Monitoring Mycophenolate Mofetil Therapy in Children with Nephrotic Syndrome"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2764-1575","authenticated-orcid":false,"given":"Joanna","family":"Sobiak","sequence":"first","affiliation":[{"name":"Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 60-781 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"J\u00f3\u017awiak","sequence":"additional","affiliation":[{"name":"Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 60-781 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honorata","family":"Wzi\u0119tek","sequence":"additional","affiliation":[{"name":"Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 60-781 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Zachwieja","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology and Hypertension, Poznan University of Medical Sciences, 60-572 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1758-8587","authenticated-orcid":false,"given":"Danuta","family":"Ostalska-Nowicka","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology and Hypertension, Poznan University of Medical Sciences, 60-572 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2165\/00003088-200746010-00002","article-title":"Clinical Pharmacokinetics and Pharmacodynamics of Mycophenolate in Solid Organ Transplant Recipients","volume":"46","author":"Staatz","year":"2007","journal-title":"Clin. Pharmacokinet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1053\/j.ackd.2009.04.003","article-title":"Kidney Transplantation: The Ideal Immunosuppression Regimen","volume":"16","author":"Yabu","year":"2009","journal-title":"Adv. Chronic Kidney Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/j.1399-0012.2005.00338.x","article-title":"Mycophenolate mofetil vs. azathioprine is associated with decreased acute rejection, late acute rejection, and risk for cardiovascular death in renal transplant recipients with pre-transplant diabetes","volume":"19","author":"David","year":"2005","journal-title":"Clin. Transplant."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1191\/0961203305LU2109OA","article-title":"Mechanisms of action of mycophenolate mofetil","volume":"14","author":"Allison","year":"2005","journal-title":"Lupus"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/j.cca.2011.08.027","article-title":"Inosine 5\u2032-monophosphate dehydrogenase activity as a biomarker in the field of transplantation","volume":"413","author":"Glander","year":"2012","journal-title":"Clin. Chim. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1517\/14656566.5.6.1333","article-title":"Review of the immunosuppressant enteric-coated mycophenolate sodium","volume":"5","author":"Budde","year":"2004","journal-title":"Expert. Opin. Pharmacother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1111\/petr.12695","article-title":"Pharmacokinetics and target attainment of mycophenolate in pediatric renal transplant patients","volume":"20","author":"Martial","year":"2016","journal-title":"Pediatr. Transplant."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.trre.2011.01.001","article-title":"Pediatric aspects of therapeutic drug monitoring of mycophenolic acid in renal transplantation","volume":"25","author":"Ettenger","year":"2011","journal-title":"Transplant. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/j.1365-2125.2012.04213.x","article-title":"Population pharmacokinetics of mycophenolic acid and dose optimization with limited sampling strategy in liver transplant children","volume":"74","author":"Barau","year":"2012","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1111\/j.1365-2125.2010.03734.x","article-title":"Population pharmacokinetics of mycophenolic acid in children and young people undergoing blood or marrow and solid organ transplantation","volume":"70","author":"Zeng","year":"2010","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1097\/01.ftd.0000159784.25872.f6","article-title":"Population Pharmacokinetics of Mycophenolic Acid in Kidney Transplant Pediatric and Adolescent Patients","volume":"27","author":"Payen","year":"2005","journal-title":"Ther. Drug Monit."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ejps.2015.06.017","article-title":"Monitoring of mycophenolate mofetil metabolites in children with nephrotic syndrome and the proposed novel target values of pharmacokinetic parameters","volume":"77","author":"Sobiak","year":"2015","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.2215\/CJN.00320116","article-title":"Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid\u2013Dependent Idiopathic Nephrotic Syndrome","volume":"11","author":"Tellier","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1097\/FTD.0000000000000258","article-title":"Mycophenolate Mofetil Therapy in Children With Idiopathic Nephrotic Syndrome","volume":"38","author":"Hackl","year":"2016","journal-title":"Ther. Drug Monit."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1177\/0091270010368542","article-title":"Inosine Monophosphate Dehydrogenase (IMPDH) Activity as a Pharmacodynamic Biomarker of Mycophenolic Acid Effects in Pediatric Kidney Transplant Recipients","volume":"51","author":"Fukuda","year":"2011","journal-title":"J. Clin. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00467-016-3352-2","article-title":"The compelling case for therapeutic drug monitoring of mycophenolate mofetil therapy","volume":"32","author":"Filler","year":"2016","journal-title":"Pediatr. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1007\/s00467-005-1964-z","article-title":"Mycophenolate mofetil therapy in frequently relapsing steroid-dependent and steroid-resistant nephrotic syndrome of childhood: Current status and future directions","volume":"20","author":"Moudgil","year":"2005","journal-title":"Pediatr. Nephrol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1007\/s00204-014-1247-1","article-title":"Pharmacology and toxicology of mycophenolate in organ transplant recipients: An update","volume":"88","author":"Staatz","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1515\/CCLM.2000.191","article-title":"Pharmacodynamic Monitoring of Mycophenolate Mofetil","volume":"38","author":"Budde","year":"2000","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_20","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":"ref_21","doi-asserted-by":"crossref","first-page":"S301","DOI":"10.1111\/j.1432-2277.2000.tb02045.x","article-title":"Pharmacokinetics and pharmacodynamics of mycophenolic acid in stable renal transplant recipients treated with low doses of mycophenolate mofetil","volume":"13","author":"Brunet","year":"2000","journal-title":"Transpl. Int."},{"key":"ref_22","first-page":"2045","article-title":"Pre-Transplant Inosine Monophosphate Dehydrogenase Activity is Associated with Clinical Outcome After Renal Transplantation","volume":"4","author":"Glander","year":"2004","journal-title":"Arab. Archaeol. Epigr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1002\/bmc.3423","article-title":"Sensitive and validated LC-MS\/MS methods to evaluate mycophenolic acid pharmacokinetics and pharmacodynamics in hematopoietic stem cell transplant patients","volume":"29","author":"Kawanishi","year":"2015","journal-title":"Biomed. Chromatogr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1097\/FTD.0b013e31819c3f3d","article-title":"Improved Assay for the Nonradioactive Determination of Inosine 5\u2032-Monophosphate Dehydrogenase Activity in Peripheral Blood Mononuclear Cells","volume":"31","author":"Glander","year":"2009","journal-title":"Ther. Drug Monit."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.cca.2018.06.042","article-title":"Optimization and application of an HPLC method for quantification of inosine-5\u2032-monophosphate dehydrogenase activity as a pharmacodynamic biomarker of mycophenolic acid in Chinese renal transplant patients","volume":"485","author":"Liu","year":"2018","journal-title":"Clin. Chim. Acta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.clinbiochem.2014.12.005","article-title":"Plasma and intracellular pharmacokinetic\u2013pharmacodynamic analysis of mycophenolic acid in de novo kidney transplant patients","volume":"48","author":"Thi","year":"2015","journal-title":"Clin. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1111\/bcp.13154","article-title":"van The pharmacokinetics and pharmacodynamics of mycophenolate mofetil in younger and elderly renal transplant recipients","volume":"83","author":"Tang","year":"2017","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_28","unstructured":"(2020, June 15). Available online: https:\/\/www.ema.europa.eu\/en\/bioanalytical-method-validation;Guideline-bioanalytical-method-validation_en.pdf."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jchromb.2007.09.036","article-title":"Liquid chromatographic determination of mycophenolic acid and its metabolites in human kidney transplant plasma: Pharmacokinetic application","volume":"859","author":"Elbarbry","year":"2007","journal-title":"J. Chromatogr. B"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/8\/200\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:02:39Z","timestamp":1760176959000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/8\/200"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,18]]},"references-count":29,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["ph13080200"],"URL":"https:\/\/doi.org\/10.3390\/ph13080200","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,18]]}}}