{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T09:16:51Z","timestamp":1773047811556,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T00:00:00Z","timestamp":1672272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>There is significant enterohepatic circulation (EHC) during the disposition of mycophenolic acid (MPA). The aim of this study was to elucidate factors influencing the EHC of MPA in Chinese adult renal allograft recipients. After 2\u00a0weeks of therapy with mycophenolate mofetil or enteric\u2010coated mycophenolate sodium, blood samples were collected from 125 patients at 0 to 12\u00a0hours post\u2010administration and MPA concentrations were determined. The influence of calcineurin inhibitors (CNIs) and genetic polymorphisms on MPA exposure and EHC was studied. The Shapley additive explanations method was used to estimate the impact of various factors on the area under the plasma drug concentration\u2013time curve (AUC<jats:sub>0\u201312h<\/jats:sub>) for MPA. An extreme gradient boosting (XGboost) machine learning\u2010based model was established to predict AUC<jats:sub>0\u201312h<\/jats:sub>. Results showed that the dose\u2010normalized AUC<jats:sub>6\u201312h<\/jats:sub> (dn\u2010AUC<jats:sub>6\u201312h<\/jats:sub>) of MPA was significantly lower in patients co\u2010administered with cyclosporine (CsA) than in patients co\u2010administered with tacrolimus (TAC) (<jats:italic>P\u00a0&lt;<\/jats:italic>\u00a0.05). For patients co\u2010administered with TAC, patients with <jats:italic>ABCC2<\/jats:italic> C\u201024T\u00a0CC or <jats:italic>SLCO1B1<\/jats:italic> T521C\u00a0TT genotypes had significantly higher values of dn\u2010AUC<jats:sub>6\u201012h<\/jats:sub> (<jats:italic>P\u00a0&lt;<\/jats:italic>\u00a0.05). Patients with <jats:italic>SLCO1B3<\/jats:italic> 334T\/699G alleles had significantly lower dn\u2010AUC<jats:sub>6\u201312h<\/jats:sub> values than homozygotes (<jats:italic>P\u00a0&lt;<\/jats:italic>\u00a0.05). By introducing body weight, age, and EHC\u2010related factors, including co\u2010administered CNIs and genetic polymorphism of drug transporters, as covariates in the XGboost machine learning model, the prediction performance of AUC<jats:sub>0\u201312h<\/jats:sub> for MPA in Chinese adult renal allograft recipients can be improved.<\/jats:p>","DOI":"10.1002\/jcph.2176","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T14:29:44Z","timestamp":1668695384000},"page":"410-420","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Influence of Calcineurin Inhibitors and Genetic Polymorphism of Transporters on Enterohepatic Circulation and Exposure of Mycophenolic Acid in Chinese Adult Renal Allograft Recipients"],"prefix":"10.1002","volume":"63","author":[{"given":"Sha\u2010Sha","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Pharmacy Ruijin Hospital Shanghai Jiao 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