{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:02:18Z","timestamp":1789624938069,"version":"build-2803163510"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontierspartnerships.org"],"crossmark-restriction":true},"short-container-title":["J. Pharm. Pharm. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mycophenolic acid (MPA), a first-line immunosuppressant for preventing transplant organ rejection, exhibits substantial inter- and intra-individual pharmacokinetic variability. We hypothesized that music elements (tempo, rhythm, and harmony) can affect the formation of MPA glucuronide (the major, inactive metabolite, MPAG) and MPA acyl glucuronide (the minor, toxic metabolite, AcMPAG) in Sprague Dawley (SD) rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>SD rats (8\u201310 weeks; 200\u2013300\u00a0g; N = 8 per group [equal sex]) were exposed for 24\u00a0h in a sound-monitored room with music combinations (fast or slow tempo with regular or irregular rhythm) versus controls. Liver microsomes were analysed for MPAG and AcMPAG formation under initial velocity conditions. As FT IR (fast tempo with irregular rhythm) significantly reduced AcMPAG formation, we further tested harmony (tonal vs. atonal [AH]) within FT IR using three independent composers and two published pieces. MPA glucuronides were quantified by liquid chromatography\u2013tandem mass spectrometry. Enzyme kinetics in FT IR AH versus controls were determined across MPA concentrations (0\u2013320\u00a0\u03bcg\/mL). mRNA and protein expression of the AcMPAG-forming enzyme (UDP-glucuronosyltransferase UGT2B1) and other expressed UGTs were analysed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MPAG formation was unaffected by any music combination, whereas niflumic acid (100\u00a0\u03bcM, positive control) reduced it by \u223c67%. AcMPAG formation was significantly reduced by FT IR (42.5 \u00b1 14.4%; mean \u00b1 SEM; p &amp;lt; 0.05) and further reduced with added AH (74.4 \u00b1 10.8%; p &amp;lt; 0.005). For MPAG,\n                      <jats:italic>V<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>max<\/jats:italic>\n                      <\/jats:sub>\n                      and\n                      <jats:italic>CL<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>int<\/jats:italic>\n                      <\/jats:sub>\n                      were comparable to controls, with a modestly higher\n                      <jats:italic>K<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>m<\/jats:italic>\n                      <\/jats:sub>\n                      . For AcMPAG,\n                      <jats:italic>V<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>max<\/jats:italic>\n                      <\/jats:sub>\n                      and\n                      <jats:italic>CL<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>int<\/jats:italic>\n                      <\/jats:sub>\n                      decreased by 89.7 \u00b1 46.4% and 91.5 \u00b1 29.7%, respectively (p &amp;lt; 0.05, n = 7 [3 males, 4 females]), with no change in\n                      <jats:italic>K<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>m<\/jats:italic>\n                      <\/jats:sub>\n                      . No sex differences in kinetic parameters were observed for either analyte. Inter-composer differences in MPA glucuronidation could be explained by the legato (continuous)-to-staccato (intermittent) articulation ratio. Hepatic\n                      <jats:italic>Ugt2b1<\/jats:italic>\n                      mRNA and protein expression were unchanged after FT IR AH exposure, as were hepatic\n                      <jats:italic>Ugt1a1, Ugt1a5, Ugt1a6, Ugt1a7,<\/jats:italic>\n                      and\n                      <jats:italic>Ugt2b12<\/jats:italic>\n                      mRNA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our novel findings indicate that specific music elements (FT IR AH) reduced generation of the minor, toxic AcMPAG without affecting formation of the major, inactive MPAG. This is potentially therapeutically beneficial, as the adverse effects of MPA might be selectively attenuated without altering its clearance or therapeutic outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/jpps.2026.17260","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:10:13Z","timestamp":1789621813000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of music elements on mycophenolate glucuronidation in rat liver microsomes"],"prefix":"10.3389","volume":"29","author":[{"given":"Jinal","family":"Adhiya","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta","place":["Edmonton, AB, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali H.","family":"Shalaby","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta","place":["Edmonton, AB, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ala\u2019A. 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