Fecal β-glucuronidase activity differs between hematopoietic cell and kidney transplantation and a possible mechanism for disparate dose requirements

粪便 β-葡萄糖醛酸酶活性在造血细胞和肾脏移植之间有所不同,以及剂量要求不同的可能机制

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作者:Mohammad Haneef Khan, Guillaume C Onyeaghala, Armin Rashidi, Shernan G Holtan, Alexander Khoruts, Ajay Israni, Pamala A Jacobson, Christopher Staley

Abstract

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.

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