Pharmacological knowledge and sustainable anthelmintic therapy in ruminants

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.