Bories Mathilde, Malnoë David, Le Corre Pascal
CHU Rennes, INSERM, LTSI-UMR 1099, Univ Rennes, Rennes, France.
Pôle Pharmacie, Secteur Pharmacotechnie et Onco-Pharmacie, Centre Hospitalier Universitaire de Rennes, Rennes, France.
Clin Transl Sci. 2025 Jun;18(6):e70260. doi: 10.1111/cts.70260.
OATP1B is a key transporter involved in hepatic drug uptake, where its inhibition can significantly increase plasma drug levels, leading to potential adverse effects. This retrospective study aimed to determine the prevalence of potential drug-drug interactions (pDDIs) mediated by the hepatic transporter OATP1B1/3 in a cohort of 44,877 patients hospitalized at Rennes Academic Medical Center, using data from the Clinical Data Warehouse. We analyzed prescription rates of OATP1B substrates and inhibitors and estimated the prevalence of pDDIs, assessed the consistency of pDDI identification across different drug interaction databases, and performed a literature review of identified OATP1B-based pDDIs. The identification of pDDIs across different drug databases showed inconsistencies, with limited overlap and variability in reported interactions. Among hospitalized patients, 6954 (15.5%) received OATP1B substrates, while 408 (0.9%) received inhibitors, leading to 106 pDDIs observed in 99 patients (0.2%). The pDDI rate varied significantly depending on the inhibitor used, reaching up to 39.1% in patients treated with ciclosporin. Statins accounted for a large proportion of pDDIs, emphasizing the potential risks, especially in multidrug regimens. Commonly involved inhibitors included FDA drugs such as ciclosporin, clarithromycin, and rifampicin. The clinical relevance of these interactions remains uncertain due to the limited availability of supporting evidence and the restricted list of well-characterized OATP1B substrates and inhibitors. This study highlights the complexity of OATP1B-mediated pDDIs and the need for increased clinical awareness and further research to improve the detection and characterization of such pDDIs, particularly for high-risk drugs with a narrow therapeutic index.
有机阴离子转运多肽1B（OATP1B）是参与肝脏药物摄取的关键转运体，抑制该转运体可显著提高血浆药物水平，从而导致潜在的不良反应。这项回顾性研究旨在利用临床数据仓库中的数据，确定在雷恩学术医学中心住院的44877名患者队列中，由肝脏转运体OATP1B1/3介导的潜在药物-药物相互作用（pDDI）的发生率。我们分析了OATP1B底物和抑制剂的处方率，估计了pDDI的发生率，评估了不同药物相互作用数据库中pDDI识别的一致性，并对已识别的基于OATP1B的pDDI进行了文献综述。不同药物数据库中pDDI的识别存在不一致性，报告的相互作用重叠有限且存在变异性。在住院患者中，6954名（15.5%）接受了OATP1B底物治疗，而408名（0.9%）接受了抑制剂治疗，导致99名患者（0.2%）出现了106次pDDI。pDDI发生率因使用的抑制剂不同而有显著差异，接受环孢素治疗的患者中pDDI发生率高达39.1%。他汀类药物在pDDI中占很大比例，突出了潜在风险，尤其是在多药治疗方案中。常见的相关抑制剂包括美国食品药品监督管理局（FDA）批准的药物，如环孢素、克拉霉素和利福平。由于支持证据有限以及特征明确的OATP1B底物和抑制剂清单受限，这些相互作用的临床相关性仍不确定。本研究强调了OATP1B介导的pDDI的复杂性，以及提高临床认识和进一步研究以改善此类pDDI的检测和特征描述的必要性，特别是对于治疗指数狭窄的高风险药物。
