Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN), CONICET, Facultad de Ciencias Veterinarias, UNCPBA, Campus Universitario, 7000 Tandil, Argentina.
Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN), CONICET, Facultad de Ciencias Veterinarias, UNCPBA, Campus Universitario, 7000 Tandil, Argentina.
Vet Parasitol. 2014 Jul 30;204(1-2):18-33. doi: 10.1016/j.vetpar.2013.11.003. Epub 2013 Nov 15.
Considering the increasing concern for the development of anthelmintic resistance, the use of pharmacology-based information is critical to design successful strategies for the future of parasite control in livestock. Integrated evaluation of the available knowledge on pharmacological features is required to optimize the activity and to achieve sustainable use of the existing anthelmintic drugs. The assessment of the drug disposition in the host and the comprehension of the mechanisms of drug influx/efflux/detoxification in different target helminths, has signified a relevant progress on the understanding of the pharmacology of anthelmintic drugs in ruminant species. However, additional scientific knowledge on how to improve the use of available and novel molecules is required to avoid/delay resistance development. Different pharmacokinetic-based approaches to enhance parasite exposure and the use of mixtures of drugs from different chemical families have been proposed as valid strategies to delay the development of anthelmintic resistance. The rationale behind using drug combinations is based on the fact that individual worms may have a lower degree of resistance to a multiple component formulation (each chemical with different mode of action/resistance) compared to that observed when a single anthelmintic is used. However, the limited available information is unclear on the potential additive or synergistic effects occurring after co-administration of two (or more) drugs with different mode of action. This review article contributes to the topic with some pharmacology-based data emerging from the assessment of combined anthelmintic preparations. The activity against multi-drug-resistant isolates based on novel modes of action is a highly favorable element to judge the future of some of the recently developed anthelmintic compounds. More specific knowledge on the basic host-parasite kinetic behavior as well as a highly responsible use of those novel compounds will be necessary to secure their maximum lifespans. Overall, the outcome from integrated pharmaco-parasitological research approaches has greatly contributed to optimize drug activity, which seems relevant to preserve existing and particularly novel active ingredients as useful tools for parasite control in livestock animals.
考虑到人们对驱虫药耐药性发展的日益关注，基于药理学的信息对于设计未来家畜寄生虫控制策略至关重要。需要综合评估现有药理学特征方面的知识，以优化药物活性并实现现有驱虫药物的可持续利用。评估药物在宿主中的分布情况，以及理解不同靶标寄生虫中药物流入/流出/解毒的机制，这标志着人们对反刍动物驱虫药药理学的理解取得了重要进展。然而，需要更多关于如何改进现有和新型分子利用的科学知识，以避免/延缓耐药性的产生。已经提出了不同的基于药代动力学的方法来增强寄生虫暴露，并使用来自不同化学家族的药物混合物作为延迟驱虫药耐药性发展的有效策略。联合用药的基本原理是基于这样一个事实，即与单一驱虫药相比，单个蠕虫对多组分配方（每种化学物质具有不同的作用方式/耐药性）的耐药性可能较低。然而，关于在联合使用两种（或更多种）具有不同作用方式的药物后可能发生的附加或协同作用，目前可用的有限信息尚不清楚。本文从评估联合驱虫制剂中获得的一些基于药理学的新数据，为该主题做出了贡献。基于新型作用方式对多药耐药分离株的活性是判断一些最近开发的驱虫化合物未来前景的一个非常有利的因素。关于基本宿主-寄生虫动力学行为的更具体知识以及对这些新型化合物的高度负责的使用，将是确保它们最大限度延长寿命所必需的。总的来说，综合药代寄生虫学研究方法的结果极大地促进了药物活性的优化，这对于保护现有特别是新型有效成分作为家畜寄生虫控制的有用工具似乎是相关的。
