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.

摘要

肠道微生物群产生 β-葡萄糖醛酸酶，该酶在免疫抑制剂霉酚酸酯 (MMF) 的代谢中起重要作用。这种药物常用于器官和造血细胞移植 (HCT)，不同移植类型的剂量不同。我们假设移植类型之间的 β-葡萄糖醛酸酶活性不同，这可能解释了剂量要求的差异。我们评估了接受 MMF 异基因 HCT 后和肾移植后患者的粪便 β-葡萄糖醛酸酶活性。肾移植患者的 β-葡萄糖醛酸酶活性 (8.48 ± 6.21 nmol/hr/g) 明显高于 HCT 患者 (3.50 ± 3.29 nmol/hr/g; P= .001)。微生物介导的 β-葡萄糖醛酸酶活性可能是进入体循环的霉酚酸酯量的关键决定因素，也是 MMF 精确给药的重要考虑因素。