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口服抗生素降低吗替麦考酚酯的药物暴露,可能通过干扰肠肝循环:一个病例系列。

Oral antibiotics lower mycophenolate mofetil drug exposure, possibly by interfering with the enterohepatic recirculation: A case series.

机构信息

Department of Hospital Pharmacy, ErasmusMC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Department of Internal Medicine, ErasmusMC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

出版信息

Pharmacol Res Perspect. 2023 Jun;11(3):e01103. doi: 10.1002/prp2.1103.

Abstract

Mycophenolate mofetil has an important role as immunosuppressive agent in solid organ transplant recipients. Exposure to the active mycophenolic acid (MPA) can be monitored using therapeutic drug monitoring. We present three cases in which MPA exposure severely decreased after oral antibiotic coadministration. By diminishing gut bacteria β-glucuronidase activity, oral antibiotics can prevent deglucuronidation of the inactive MPA-7-O-glucuronide metabolite to MPA and thereby possibly prevent its enterohepatic recirculation. This pharmacokinetic interaction could result in rejection, which makes it clinically relevant in solid organ transplant recipients, especially when therapeutic drug monitoring frequency is low. Routine screening for this interaction, preferably supported by clinical decision support systems, and pragmatic close monitoring of the MPA exposure in cases is advised.

摘要

霉酚酸酯在实体器官移植受者中作为免疫抑制剂具有重要作用。可以使用治疗药物监测来监测活性麦考酚酸(MPA)的暴露情况。我们报告了三例在口服抗生素合用后 MPA 暴露严重减少的病例。通过减少肠道细菌β-葡萄糖醛酸酶的活性,口服抗生素可以防止无活性的 MPA-7-O-葡萄糖醛酸代谢物脱葡萄糖醛酸化为 MPA,从而可能阻止其肠肝再循环。这种药代动力学相互作用可能导致排斥反应,这在实体器官移植受者中具有临床相关性,特别是在治疗药物监测频率较低时。建议在临床上进行这种相互作用的常规筛查,最好有临床决策支持系统的支持,并在病例中对 MPA 暴露情况进行实际密切监测。

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