已经批准了多种癌症治疗的聚腺苷二磷酸核糖聚合酶（PARP）抑制剂。它们具有相似的作用机制，但在药代动力学特性和药物间相互作用（DDI）方面存在差异。该研究评估了PARP抑制剂（尼拉帕尼、奥拉帕尼和鲁卡帕尼）与他汀类药物（阿托伐他汀和瑞舒伐他汀）之间的潜在ATP结合盒转运蛋白介导的相互作用。我们使用囊泡转运实验研究了PARP抑制剂对乳腺癌耐药蛋白（BCRP）、多药耐药相关蛋白3（MRP3）和P-糖蛋白（P-gp）的抑制活性，并确定了50%抑制所需的浓度（IC50）。然后，我们使用机械静态模型预测了PARP抑制剂给药后他汀类药物暴露增加的情况。鲁卡帕尼是BCRP介导的瑞舒伐他汀转运的最强抑制剂（IC50为13.7μM），其次是尼拉帕尼（42.6μM）和奥拉帕尼（216μM）。PARP抑制剂不影响MRP3。尽管尼拉帕尼似乎能抑制P-gp，但抑制作用存在较大变异性。预测鲁卡帕尼、尼拉帕尼和奥拉帕尼对肠道BCRP的抑制将分别使瑞舒伐他汀的曝光增加52%、37%和24%。PARP抑制剂与瑞舒伐他汀之间的相互作用可能单独对临床意义较小，但结合其他易感因素可能会增加瑞舒伐他汀相关的不良反应风险。本文受版权保护。保留所有权利。

Poly ADP-ribose polymerase (PARP) inhibitors have been approved for the treatment of various cancers. They share similar mechanism of action, but have differences in pharmacokinetic characteristics and potential for drug-drug interactions (DDI). This study evaluated the potential ATP-binding cassette transporter-mediated interactions between PARP inhibitors (niraparib, olaparib, and rucaparib) and statins (atorvastatin and rosuvastatin). We studied the inhibitory activity of PARP inhibitors on breast cancer resistance protein (BCRP), multidrug resistance-associated protein 3 (MRP3), and P-glycoprotein (P-gp) using vesicular transport assays and determined the concentrations required for 50% inhibition (IC50 ). Then, we predicted the increase of statin exposure followed by the administration of PARP inhibitors using a mechanistic static model. Rucaparib was the strongest inhibitor of BCRP-mediated rosuvastatin transport (IC50 13.7 μM), followed by niraparib (42.6 μM) and olaparib (216 μM). PARP inhibitors did not affect MRP3. While niraparib appeared to inhibit P-gp, the inhibition showed large variability. The inhibition of intestinal BCRP by rucaparib, niraparib and olaparib was predicted to elevate rosuvastatin exposure by 52%, 37%, and 24%, respectively. The interactions between PARP inhibitors and rosuvastatin are probably of minor clinical significance alone, but combined with other predisposing factors they may increase the risk of rosuvastatin-associated adverse effects.This article is protected by copyright. All rights reserved.