{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:42:43Z","timestamp":1791315763308,"version":"4.3.1"},"reference-count":47,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T00:00:00Z","timestamp":1661731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Some studies have shown that the area under the concentration\u2010time curve (AUC) of mycophenolic acid (MPA) should be higher for children with nephrotic syndrome (NS) than after renal transplantation. The pharmacodynamic aspect of MPA, the activity of inosine monophosphate dehydrogenase (IMPDH), has not been studied in children with NS. The study included 21 children (4\u201016\u2009years old) with NS treated with mycophenolate mofetil. MPA and its glucuronide plasma concentrations were determined using validated high\u2010performance liquid chromatography\u2010ultraviolet (HPLC\u2010UV). The separate HPLC\u2010UV method was applied for IMPDH activity determination. The variability was expressed by the coefficient of variation (CV). IMPDH activity and MPA concentration (<jats:italic>C<\/jats:italic><jats:sub>trough<\/jats:sub>) before the morning dose amounted to 29.95\u2009\u03bcmol\u2009s<jats:sup>\u22121<\/jats:sup>\u00a0mol<jats:sup>\u22121<\/jats:sup> adenosine monophosphate (AMP) (range, 6.71\u201098.60\u2009\u03bcmol\u2009s<jats:sup>\u22121<\/jats:sup>\u00a0mol<jats:sup>\u22121<\/jats:sup> AMP) and 1.72\u2009\u03bcg\/mL (range, 0.39\u20104.34\u2009\u03bcg\/mL), respectively, whereas the area under the effect\u2013time curve from 0 to 4\u00a0h and MPA AUC<jats:sub>0\u20104<\/jats:sub> were 130.36\u2009\u03bcmol\u2009s<jats:sup>\u22121<\/jats:sup>\u00a0mol<jats:sup>\u22121<\/jats:sup>AMP \u00d7 h (range, 23.58\u2010306.57\u2009\u03bcmol\u2009s<jats:sup>\u22121<\/jats:sup>\u00a0mol<jats:sup>\u22121<\/jats:sup> AMP \u00d7 h) and 24.63\u2009\u03bcg\u2009h\/mL (range, 12.21\u201067.48\u2009\u03bcg\u2009h\/mL), respectively. IMPDH activity decreased concomitantly with MPA concentration increase, however, the variability of the pharmacodynamic parameters was greater than of the pharmacokinetics. The median degree of maximum IMPDH inhibition was 61%. MPA <jats:italic>C<\/jats:italic><jats:sub>trough<\/jats:sub> and predicted AUC were lower than in our previous study. Only a few MPA pharmacokinetic parameters correlated with the pharmacodynamics. IMPDH activity did not correlate with the children's age and did not differ between boys and girls. MPA clearance was the highest in younger children (median, 10.54\u2009L\/m<jats:sup>2<\/jats:sup>\/h) and cholesterol correlated negatively with the children's age (<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u22120.659, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.003). IMPDH minimum activity and the degree of maximum IMPDH inhibition were similar to those obtained in renal transplant recipients. IMPDH activity does not undergo developmental or gender\u2010specific regulation in children with NS. MPA underexposure might be more frequent in younger children, especially with high cholesterol and triglycerides levels because of high MPA clearance.<\/jats:p>","DOI":"10.1111\/1440-1681.13706","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T18:52:33Z","timestamp":1658775153000},"page":"1197-1208","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inosine monophosphate dehydrogenase activity and mycophenolate pharmacokinetics in children with nephrotic syndrome treated with mycophenolate mofetil"],"prefix":"10.1111","volume":"49","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  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matylda","family":"Resztak","sequence":"additional","affiliation":[{"name":"Department of Physical Pharmacy and Pharmacokinetics Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Zachwieja","sequence":"additional","affiliation":[{"name":"Department of Paediatric Nephrology and Hypertension Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danuta","family":"Ostalska\u2010Nowicka","sequence":"additional","affiliation":[{"name":"Department of Paediatric Nephrology and Hypertension Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200746010-00002"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.00320116"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0039-8"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000258"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-016-3352-2"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-018-3970-y"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.07111009"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2015.06.017"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-019-02701-5"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2014.12.005"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010368542"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-011-1203-4"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13704"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.05.032"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31803d37b6"},{"issue":"2","key":"e_1_2_7_17_1","first-page":"7","article-title":"Pharmacodynamic 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