{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:43:49Z","timestamp":1787060629291,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T00:00:00Z","timestamp":1660780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Study Objective<\/jats:title>\n                    <jats:p>\n                      Mycophenolate mofetil (MMF) is the gold\u2010standard immunosuppressive agent in heart transplantation (HT), but dose\u2010dependent toxicities (e.g., neutropenia) are frequent. Gut bacteria \u03b2\u2010\n                      <jats:sc>d<\/jats:sc>\n                      \u2010glucuronidases (GUS) modulate MMF bioavailability, and changes in the intestinal flora may influence the pharmacokinetics of MMF. The objective of this study was to evaluate the safety and efficacy of MMF 1.5 g every 12 h (q12) [high\u2010dose, HD] versus 1 g q12 [low\u2010dose, LD] and explore the association between neutropenia and GUS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>We compared the incidence of acute cellular rejection (ACR) and neutropenia during the first 6\u2009months post\u2010HT. The association between neutropenia and GUS was investigated in an exploratory analysis on a subset of patients with prospectively collected stool data. Stool samples were analyzed using 16S rRNA sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Results<\/jats:title>\n                    <jats:p>\n                      A total of 168 patients (120\u2009MMF\u2010HD, 48\u2009MMF\u2010LD; mean age 55.7\u2009years, 79% male) were studied. Neutropenia occurred in 38.6% of patients at a median of 106 [64\u2013143] days. Freedom from neutropenia was lower in MMF\u2010HD compared with MMF\u2010LD (57% vs. 73%,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.03). ACR (\u22651R\/1B) occurred in 37.5% of patients at a median of 20 [10\u201396] days, while high\u2010grade ACR (\u22652R\/3A) occurred in 11.3% at a median of 14 [9\u201389] days. Freedom from ACR was similar between groups. MMF\u2010LD was associated with more high\u2010grade ACR (hazard ratio [HR] 3.47, 95% confidence interval [CI] 1.09\u201311.08,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.03) during the first month, but less neutropenia (HR 0.54, 95% CI 0.29\u20131.00,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.05) between 1 and 6\u2009months. GUS\u2010producing bacteria were more abundant in neutropenic patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MMF\u2010LD was associated with higher rates of early high\u2010grade ACR and lower rates of later neutropenia. Further studies are warranted to test whether temporal MMF dose adjustments and gut microbial composition could improve clinical outcomes post\u2010HT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/phar.2724","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T13:23:21Z","timestamp":1659705801000},"page":"697-706","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Temporal shifts in safety and efficacy profile of mycophenolate mofetil 2\u2009g versus 3\u2009g daily early after heart transplantation"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5225-8252","authenticated-orcid":false,"given":"Lorenzo","family":"Braghieri","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Cleveland Clinic  Cleveland Ohio USA"},{"name":"Division of Cardiology Department of Medicine, Columbia University  New York New York 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