{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:03:34Z","timestamp":1791479014078,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T00:00:00Z","timestamp":1749859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>\n                    Pharmacomicrobiomics is an emerging field due to important microbiome effects on pharmacokinetics and clinical outcomes. However, the application of this knowledge remains limited. Mycophenolic acid (MPA) is the primary active metabolite of the immunosuppressant, mycophenolate mofetil (MMF). MPA undergoes glucuronidation to form MPA glucuronide (MPAG) which is deglucuronidated by bacterial \u03b2\u2010glucuronidases and reformed as MPA through enterohepatic circulation (EHC). We studied the stool microbiome effect on the pharmacokinetics of MPA, its metabolites, and EHC in hematopoietic cell transplant (HCT) recipients using a semi\u2010mechanistic population pharmacokinetic model. Microbiome communities were identified using correlation network analysis, and their impact on pharmacokinetics was assessed using full fixed\u2010effects modeling. Simulations were then conducted to evaluate MMF dosing regimens and to assess the impact of community abundance on EHC and MPA therapeutic target achievement. High abundance of\n                    <jats:italic>Bacteroides uniformis<\/jats:italic>\n                    \u2010dominant and\n                    <jats:italic>Bacteroides vulgatus<\/jats:italic>\n                    \u2010dominant communities was associated with higher EHC and an increase in MPA exposure. Low abundance of these communities was associated with a 52\u201380% and 4\u201383% lower EHC and MPA exposure, respectively. Simulations showed 70% of individuals with low abundance of these communities achieved the therapeutic target at the typical HCT MMF dose of 1,000\u2009mg Q8 hours IV; however, \u2265\u200995% were within the therapeutic target at 1,250\u2009mg Q8 hours or 1,750\u2009mg Q12 hours. EHC accounted for 34% of the MPA area under the curve. Elimination of EHC reduced troughs by 100%. This work quantifies the microbiome\u2019s effect on pharmacokinetics, paving the way for future microbiome\u2010informed dosing to optimize therapeutic target attainment.\n                  <\/jats:p>","DOI":"10.1002\/cpt.3740","type":"journal-article","created":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T13:45:15Z","timestamp":1749908715000},"page":"1477-1488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Microbiome\u2010Informed Dosing: Exploring Gut Microbial Communities Impact on Mycophenolate Enterohepatic Circulation and Therapeutic Target Achievement"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8280-1375","authenticated-orcid":false,"given":"Abdelrahman","family":"Saqr","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7493-4784","authenticated-orcid":false,"given":"Shen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5458-0712","authenticated-orcid":false,"given":"Mahmoud","family":"Al\u2010Kofahi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota  Minneapolis Minnesota USA"},{"name":"Gilead Sciences, Inc.  Foster City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2309-0083","authenticated-orcid":false,"given":"Christopher","family":"Staley","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Minnesota Medical School  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4145-7045","authenticated-orcid":false,"given":"Pamala A.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,14]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.001"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat9931"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.065698"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.121.000476"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200746010-00002"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-016-0378-6"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.001651"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199834060-00002"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R116.767434"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000871"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.745"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14354"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2005.08.009"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10030406"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2021.06.001"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax2358"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2022.04.018"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-02-554725"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007158"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1900623"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2016.1250982"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix699"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2015.16"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020001531"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002677"},{"key":"e_1_2_11_26_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2022-073654","article-title":"Race\u2010free estimated glomerular filtration rate equation in kidney transplant recipients: development and validation study","volume":"381","author":"Raynaud M.","year":"2023","journal-title":"BMJ"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1088\/1742-5468\/2008\/10\/P10008"},{"key":"e_1_2_11_28_1","unstructured":"Gastonguay M.R.\u201cFull covariate models as an alternative to methods relying on statistical significance for inferences about covariate effects: a review of methodology and 42 case studies.\u201d<https:\/\/www.page\u2010meeting.org\/?abstract=2229>. 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