It is now widely accepted that organic anion-transporting polypeptides (OATPs), especially members of the OATP1A/1B family, can have a major impact on the disposition and elimination of a variety of endogenous molecules and drugs. Owing to their prominent expression in the sinusoidal plasma membrane of hepatocytes, OATP1B1 and OATP1B3 play key roles in the hepatic uptake and plasma clearance of a multitude of structurally diverse anti-cancer and other drugs. Here, we present a thorough assessment of the currently available OATP1A and OATP1B knockout and transgenic mouse models as key tools to study OATP functions in vivo. We discuss recent studies using these models demonstrating the importance of OATPs, primarily in the plasma and hepatic clearance of anticancer drugs such as taxanes, irinotecan/SN-38, methotrexate, doxorubicin, and platinum compounds. We further discuss recent work on OATP-mediated drug–drug interactions in these mouse models, as well as on the role of OATP1A/1B proteins in the phenomenon of hepatocyte hopping, an efficient and flexible way of liver detoxification for both endogenous and exogenous substrates. Interestingly, glucuronide conjugates of both the heme breakdown product bilirubin and the protein tyrosine kinase-targeted anticancer drug sorafenib are strongly affected by this process. The clinical relevance of variation in OATP1A/1B activity in patients has been previously revealed by the effects of polymorphic variants and drug–drug interactions on drug toxicity. The development of in vivo tools to study OATP1A/1B functions has greatly advanced our mechanistic understanding of their functional role in drug pharmacokinetics, and their implications for therapeutic efficacy and toxic side effects of anticancer and other drug treatments.

现已广泛接受的是，有机阴离子运输多肽（OATP），尤其是OATP1A / 1B家族的成员，可以对各种内源性分子和药物的配置和消除产生重大影响。由于OATP1B1和OATP1B3在肝细胞的正弦质膜中的显着表达，它们在多种结构多样的抗癌药和其他药物的肝摄取和血浆清除中起着关键作用。在这里，我们对当前可用的OATP1A和OATP1B敲除和转基因小鼠模型进行全面评估，作为研究体内OATP功能的关键工具。我们讨论使用这些模型的最新研究，这些研究证明了OATP的重要性，主要是在抗癌药物（如紫杉烷，伊立替康/ SN-38，甲氨蝶呤，阿霉素和铂化合物）的血浆和肝清除方面。我们进一步讨论了在这些小鼠模型中OATP介导的药物相互作用的最新工作，以及OATP1A / 1B蛋白在肝细胞跳动现象中的作用，这是一种对内源性和外源性底物进行有效且灵活的肝脏排毒方法。有趣的是，血红素分解产物胆红素和以蛋白质酪氨酸激酶为靶点的抗癌药物索拉非尼的葡糖醛酸结合物都受到这一过程的强烈影响。多态性变体和药物相互作用对药物毒性的影响以前已经揭示了患者OATP1A / 1B活性变化的临床意义。的发展用于研究OATP1A / 1B功能的体内工具极大地提高了我们对它们在药物药代动力学中的功能作用及其对抗癌药和其他药物治疗的疗效和毒性副作用的影响的机械理解。