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

IF 2.9 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Mirjam Simoons, Kishan A T Naipal, Huib de Jong, Caroline M den Hoed, Brenda C M de Winter, Midas B Mulder
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引用次数: 2

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.

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口服抗生素降低霉酚酸酯药物暴露,可能通过干扰肠肝再循环:一个病例系列。
霉酚酸酯在实体器官移植受者中具有重要的免疫抑制剂作用。暴露于活性霉酚酸(MPA)可以监测使用治疗药物监测。我们报告了三个病例,其中MPA暴露严重减少口服抗生素联合用药后。口服抗生素通过降低肠道细菌β-葡糖醛酸酶活性,阻止无活性的MPA-7- o -葡糖醛酸代谢物去糖醛酸化为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,这使得它在实体器官移植受者中具有临床意义,特别是当治疗药物监测频率较低时。建议对这种相互作用进行常规筛查,最好得到临床决策支持系统的支持,并对病例中的MPA暴露情况进行务实的密切监测。
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来源期刊
Pharmacology Research & Perspectives
Pharmacology Research & Perspectives Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
5.30
自引率
3.80%
发文量
120
审稿时长
20 weeks
期刊介绍: PR&P is jointly published by the American Society for Pharmacology and Experimental Therapeutics (ASPET), the British Pharmacological Society (BPS), and Wiley. PR&P is a bi-monthly open access journal that publishes a range of article types, including: target validation (preclinical papers that show a hypothesis is incorrect or papers on drugs that have failed in early clinical development); drug discovery reviews (strategy, hypotheses, and data resulting in a successful therapeutic drug); frontiers in translational medicine (drug and target validation for an unmet therapeutic need); pharmacological hypotheses (reviews that are oriented to inform a novel hypothesis); and replication studies (work that refutes key findings [failed replication] and work that validates key findings). PR&P publishes papers submitted directly to the journal and those referred from the journals of ASPET and the BPS
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