Department of Transplant Surgery, Brigham and Women's Hospital, Boston, MA, USA.
Ann Pharmacother. 2012 Jul-Aug;46(7-8):1054-64. doi: 10.1345/aph.1R071. Epub 2012 Jul 17.
To evaluate the incidence of gastrointestinal (GI) complications in solid organ transplant (SOT) recipients, impact of the complications on transplant outcomes, and the potential interactions between mycophenolic acid (MPA) derivatives and proton pump inhibitors (PPIs).
An unrestricted literature search (1980-January 2012) was performed with MEDLINE and EMBASE using the following key words: drug-drug interaction, enteric-coated mycophenolic acid, GI complications, mycophenolate mofetil, solid organ transplant, and proton pump inhibitor, including individual agents within the class. Abstracts from scientific meetings were also evaluated. Additionally, reference citations from identified publications were reviewed.
Relevant English-language, original research articles and review articles were evaluated if they focused on any of the topics identified in the search or included substantial content addressing GI complications in SOT recipients or drug interactions.
GI complications are frequent among SOT recipients, with some studies showing prevalence rates as high as 70%. Transplant outcomes among renal transplant recipients are significantly impacted by GI complications, especially in patients requiring immunosuppressant dosage reductions or premature discontinuation. To this end, PPI use among patients receiving transplants is common. Recent data demonstrate that PPIs significantly reduce the overall exposure to MPA after oral administration of mycophenolate mofetil. Similar studies show this interaction does not exist between PPIs and enteric-coated mycophenolic acid (EC-MPA). Unfortunately, most of the available data evaluating this interaction are pharmacokinetic analyses that do not investigate the clinical impact of this interaction.
A significant interaction exists between PPIs and mycophenolate mofetil secondary to reduced dissolution of mycophenolate mofetil in higher pH environments. EC-MPA is not absorbed in the stomach; therefore, low intragastric acidity does not impact EC-MPA and bioavailability is maintained with this formulation during PPI coadministration. The clinical impact of this interaction is unknown, yet one can theorize that reduced exposure to MPA in SOT recipients can increase the risk of allograft rejection and/or failure.
评估实体器官移植（SOT）受者胃肠道（GI）并发症的发生率、并发症对移植结果的影响，以及麦考酚酸（MPA）衍生物和质子泵抑制剂（PPIs）之间的潜在相互作用。
使用 MEDLINE 和 EMBASE 进行了无限制的文献检索（1980 年-2012 年 1 月），使用了以下关键词：药物-药物相互作用、肠包衣麦考酚酸、GI 并发症、麦考酚酸酯莫福丁、实体器官移植和质子泵抑制剂，包括该类别的单个药物。还评估了科学会议的摘要。此外，还审查了已确定出版物的参考文献。
如果符合以下条件，则评估相关的英文原始研究文章和综述文章：重点关注搜索中确定的任何主题，或包含实质性内容，涉及 SOT 受者的 GI 并发症或药物相互作用。
GI 并发症在 SOT 受者中很常见，有些研究显示患病率高达 70%。GI 并发症对肾移植受者的移植结果有显著影响，尤其是在需要减少免疫抑制剂剂量或提前停药的患者中。为此，接受移植的患者常使用 PPI。最近的数据表明，PPIs 显著降低了口服麦考酚酸酯莫福丁后的 MPA 总体暴露量。类似的研究表明，PPIs 与肠包衣麦考酚酸（EC-MPA）之间不存在这种相互作用。不幸的是，评估这种相互作用的大部分可用数据都是药代动力学分析，并未调查这种相互作用的临床影响。
由于较高 pH 环境下麦考酚酸酯莫福丁的溶解减少，PPIs 和麦考酚酸酯莫福丁之间存在显著相互作用。EC-MPA 不会在胃中吸收；因此，低胃内酸度不会影响 EC-MPA，并且在与 PPI 联合给药时，该制剂保持生物利用度。这种相互作用的临床影响尚不清楚，但人们可以推断，SOT 受者中 MPA 暴露减少会增加移植物排斥和/或失败的风险。
