The intestinal microbiota produces β-glucuronidase that plays an essential role in the metabolism of the immunosuppressant mycophenolate mofetil (MMF). This drug is commonly used in organ and hematopoietic cell transplantation (HCT), with variations in dosing across transplant types. We hypothesized that β-glucuronidase activity differs between transplant types, which may account for differences in dosing requirements. We evaluated fecal β-glucuronidase activity in patients receiving MMF post-allogeneic HCT and post-kidney transplant. Kidney transplant patients had significantly greater β-glucuronidase activity (8.48 ± 6.21 nmol/hr/g) than HCT patients (3.50 ± 3.29 nmol/hr/g; P = .001). Microbially mediated β-glucuronidase activity may be a critical determinant in the amount of mycophenolate entering the systemic circulation and an important factor to consider for precision dosing of MMF.
Bibliographical noteFunding Information:
The HCT study was supported by a University of Minnesota, Masonic Cancer Center Chainbreaker award, NIH grant P30CA077598, and the National Center for Advancing Translational Sciences of the National Institutes of Health P30CA077598, UL1-TR00249, R01AI140303 Award Number UL1-TR00249. The MISSION study was supported by NIH R01AI140303 from the NIAID. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health; Masonic Cancer Center, University of Minnesota;
© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.
- intestinal microbiota