Laboratorio de Farmacología, Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, UNCPBA, Campus Universitario, 7000 Tandil, Argentina.
Curr Pharm Biotechnol. 2012 May;13(6):912-23. doi: 10.2174/138920112800399211.
Macrocyclic lactones (MLs) are antiparasitic drugs used against endo-ectoparasites. Regarding the wide use of MLs in different species, it is likely that drug-drug interactions may occur after their co-administration with other compounds. A new paradigm was introduced in the study of the pharmacology of MLs during the last years since the interactions of MLs with ATP-binding cassete (ABC) transporters have been described. The current review article gives an update on the available information concerning drug-drug interactions involving the MLs. The basis of the methodological approaches used to evaluate transport interactions, and the impact of the pharmacology-based modulation of drug transport on the MLs disposition kinetics and clinical efficacy, are discussed in an integrated manner. A different number of in vitro and ex vivo methods have been reported to study the characterization of the interactions between MLs and ABC transporters. The production of the ABC transporters knockout mice has provided valuable in vivo tools to study this type of drug-drug interaction. In vivo trials performed in different species corroborated the effects of ABC transporter modulators on the pharmacokinetics behaviour of MLs. Important pharmacokinetic changes on plasma disposition of MLs have been observed when these compounds are co-administered with P-glycoprotein modulators. The modulation of the activity of P-glycoprotein was evaluated as a strategy not only to increase the systemic availability of MLs but also to improve their clinical efficacy. The understanding of the MLs interactions may supply relevant information to optimize their use in veterinary and human therapeutics.
大环内酯类（MLs）是用于治疗内寄生虫和外寄生虫的抗寄生虫药物。鉴于 MLs 在不同物种中的广泛应用，在与其他化合物联合使用时，可能会发生药物相互作用。在过去几年中，由于 MLs 与三磷酸腺苷结合盒（ABC）转运蛋白的相互作用已被描述，因此在 MLs 药理学研究中引入了一个新的范例。本文综述了有关涉及 MLs 的药物相互作用的现有信息。本文以综合的方式讨论了评估转运相互作用的方法学方法的基础，以及基于药理学的药物转运调节对 MLs 处置动力学和临床疗效的影响。已经报道了许多不同的体外和体内方法来研究 MLs 与 ABC 转运蛋白之间相互作用的特征。ABC 转运体敲除小鼠的产生为研究这种类型的药物相互作用提供了有价值的体内工具。在不同物种中进行的体内试验证实了 ABC 转运体调节剂对 MLs 药代动力学行为的影响。当这些化合物与 P-糖蛋白调节剂联合使用时，观察到对 MLs 血浆处置的重要药代动力学变化。P-糖蛋白活性的调节不仅被评估为增加 MLs 的全身可用性的策略，而且还被评估为提高其临床疗效的策略。对 MLs 相互作用的了解可能会提供有关信息，以优化其在兽医和人类治疗中的应用。
