{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T05:16:34Z","timestamp":1779081394155,"version":"3.51.4"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T00:00:00Z","timestamp":1533600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Although therapeutic drug monitoring of plasma mycophenolic acid (MPA) concentrations has been recommended to individualize dosage in transplant recipients, little is known regarding lymphocyte concentrations of MPA, where MPA inhibits inosine monophosphate dehydrogenase (IMPDH). This study investigated the utility of measuring predose MPA concentrations in peripheral blood mononuclear cells (C<jats:sub>0C<\/jats:sub>) and predose IMPDH activity, as predictors of graft rejection in renal transplant recipients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Forty\u2010eight patients commencing mycophenolate mofetil (1\u00a0g twice daily) in combination with tacrolimus and prednisolone were recruited. Blood was collected for determination of trough total (C<jats:sub>0P<\/jats:sub>) and unbound (C<jats:sub>0u<\/jats:sub>) plasma MPA concentrations. Peripheral blood mononuclear cells were isolated for determination of C<jats:sub>0C<\/jats:sub> and IMPDH activity. The incidence of rejection within 2\u00a0days of sample collection was determined histologically and classified according to the Banff 2007 criteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was no association between MPA C<jats:sub>0C<\/jats:sub> and C<jats:sub>0P<\/jats:sub> (r<jats:sub>s<\/jats:sub>\u00a0=\u00a00.28, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.06), however, MPA C<jats:sub>0C<\/jats:sub> were weakly correlated with MPA C<jats:sub>0u<\/jats:sub> (r<jats:sub>s<\/jats:sub>\u00a0=\u00a00.42, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.013). Multivariate analysis indicated that MPA C<jats:sub>0C<\/jats:sub> was the only covariate independently associated with rejection (FDR\u2010adjusted <jats:italic>P<\/jats:italic>\u00a0=\u00a00.033). The receiver operating characteristic area under the curve (AUC) for the prediction of severe rejection using MPA C<jats:sub>0C<\/jats:sub> was 0.75 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.013), with 73% sensitivity and specificity at a C<jats:sub>0C<\/jats:sub> threshold of 0.5\u00a0ng\u00a010<jats:sup>\u20137<\/jats:sup> cells. However, predose IMPDH activity was not a predictor of rejection (<jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.15).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MPA C<jats:sub>0C<\/jats:sub> measurement within the early post\u2010transplant period may be useful to facilitate early titration of MPA dosing to significantly reduce rejection.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13704","type":"journal-article","created":{"date-parts":[[2018,7,3]],"date-time":"2018-07-03T01:44:39Z","timestamp":1530582279000},"page":"2433-2442","source":"Crossref","is-referenced-by-count":19,"title":["Mycophenolic acid concentrations in peripheral blood mononuclear cells are associated with the incidence of rejection in renal transplant recipients"],"prefix":"10.1111","volume":"84","author":[{"given":"Zaipul I.","family":"Md Dom","sequence":"first","affiliation":[{"name":"Discipline of Pharmacology, Adelaide Medical School The University of Adelaide  Adelaide SA 5005 Australia"},{"name":"Department of Clinical Pharmacology The Queen Elizabeth Hospital  Woodville SA 5011 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet K.","family":"Coller","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology, Adelaide Medical School The University of Adelaide  Adelaide SA 5005 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert P.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Centre for Clinical and Experimental Transplantation, Central Northern Adelaide Renal and Transplantation Service Royal Adelaide Hospital  Adelaide SA 5000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Tuke","sequence":"additional","affiliation":[{"name":"School of Mathematical Sciences The University of Adelaide  Adelaide SA 5005 Australia"},{"name":"ARC Centre of Excellence for Mathematical &amp; Statistical Frontiers, School of Mathematical Sciences The University of Adelaide  Adelaide SA 5005 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brett C.","family":"McWhinney","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Pathology Queensland Royal Brisbane and Women's Hospital  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew A.","family":"Somogyi","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology, Adelaide Medical School The University of Adelaide  Adelaide SA 5005 Australia"},{"name":"Department of Clinical Pharmacology Royal Adelaide Hospital  Adelaide SA 5000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0186-3073","authenticated-orcid":false,"given":"Benedetta C.","family":"Sallustio","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology, Adelaide Medical School The University of Adelaide  Adelaide SA 5005 Australia"},{"name":"Department of Clinical Pharmacology The Queen Elizabeth Hospital  Woodville SA 5011 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,8,7]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"ANZDATA Registry.39th Report Chapter 8: Transplantation. Australia and New Zealand Dialysis and Tansplant Registry Adelaide Australia.2016. Available athttp:\/\/www.anzdata.org.au(last accessed 14 December 2017)."},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)74247-1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.07111009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ftd.0000199358.80013.bd"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-200108000-00001"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-1345(01)02190-X"},{"key":"e_1_2_9_8_1","first-page":"400","article-title":"Cyclosporine lymphocyte maximum level monitoring in de novo kidney transplant patients: a prospective study","volume":"4","author":"Barbari AG","year":"2006","journal-title":"Exp Clin Transplant"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2007.01.039"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e31815feede"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-2277.2011.01365.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e3181905aaa"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2013.09.009"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2014.12.005"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2014.01.006"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(00)01026-2"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010368542"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2004.00617.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.DMPK-12-RG-048"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-011-1203-4"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e3181b7a9d0"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13154"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2005.05.008"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2008.02159.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000235533.29300.e7"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1086\/319501"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2010.20"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2013.11.056"},{"key":"e_1_2_9_29_1","unstructured":"Guidance for Industry: Bioanalytical Method Validation. US Food and Drug Administration Center for Drug Evaluation and Research. 2001. Available athttp:\/\/www.fda.gov\/ucm\/groups\/fdagov\u2010public\/@fdagov\u2010drugs\u2010gen\/documents\/document\/ucm070107.pdf(last accessed 14 December 2017)."},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31819c3f3d"},{"key":"e_1_2_9_31_1","unstructured":"R Core Team.R: A language and environment for statistical computing. R Foundation for Statistical Computing. In Vienna Austria URL. Available athttp:\/\/www.r-project.org\/ 2017(last accessed 14 December 2017)."},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13877"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13883"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2003.12.009"},{"key":"e_1_2_9_36_1","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1093\/clinchem\/47.7.1241","article-title":"Pharmacokinetic basis for the efficient and safe use of low\u2010dose mycophenolate mofetil in combination with tacrolimus in kidney transplantation","volume":"47","author":"Mourad M","year":"2001","journal-title":"Clin Chem"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ftd.0000162231.90811.38"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/41.7.1011"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2004.02235.x"},{"key":"e_1_2_9_40_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1681\/ASN.V133759","article-title":"The pharmacokinetic\u2010pharmacodynamic relationship for total and free mycophenolic acid in pediatric renal transplant recipients: a report of the German study group on mycophenolate mofetil therapy","volume":"13","author":"Weber LT","year":"2002","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-2498(00)00525-8"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.9.2451.2451"},{"key":"e_1_2_9_43_1","doi-asserted-by":"crossref","first-page":"984","DOI":"10.4049\/jimmunol.152.3.984","article-title":"Effects of human T lymphocyte activation on inosine monophosphate dehydrogenase expression","volume":"152","author":"Dayton JS","year":"1994","journal-title":"J Immunol"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcp.13704","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.13704","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T11:02:08Z","timestamp":1694948528000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.13704"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,7]]},"references-count":42,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1111\/bcp.13704"],"URL":"https:\/\/doi.org\/10.1111\/bcp.13704","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,7]]}}}