Modifying the formulation or delivery mechanism to increase the activity of anthelmintic compounds

Abstract

The development of resistance to current chemical classes of broad-spectrum anthelmintics poses an undeniable threat to the long-term viability of the animal health industry. Alternative treatment strategies including vaccines, biological control and breeding of parasite-resistant animals are unlikely to be widely available in the near future and even then, they will be integrated with chemotherapy. To compound the severity of the situation there appears to be no new chemical class of anthelmintics, with unique mode of action, on the horizon. The significant cost of drug research and the development costs of a drug that is to be used in food-producing animals, together with the small market share of animal health products compared to human pharmaceutical/medical and cosmetic products, provide little incentive for anthelmintic development. The chemical actives that are currently available, are all that we are likely to have for the foresseable future. If effective parasite treatment is to continue, existing actives must be used more efficiently. Recognising the potential for the animal's physiological behaviour to assist drug action is of significant value. Reduction of feed intake before oral anthelmintic treatment slows ruminant digesta flow, prolongs and extends the availability and therefore increases efficacy, of the benzimidazole and ivermectin compounds. This is a cost effective option that can be employed which not only increases efficacy of ‘older’ compounds, but will be instrumental in prolonging the useful life of the ‘newer’ drugs. In a related approach the co-administration of metabolic inhibitors can prolong drug clearance and extend availability and increase the action of existing anthelmintics. However, given the large costs which would be associated with this development (host toxicity, residue safety) it is probable that the value of such combinations would be more appropriate for use in the treatment of non-food producing animals. The most promising approach for improved formulation lies in innovative delivery system using chemical or physical carrier. Solubility-defining salts, oils, solid/drug matrices, liposomes and related microparticles that reduce drug absorption/metabolism and can specificantly direct large quantities of active, over an extended or pre-determined period, to the site(s) of parasitic infection. The use of lipophilic actives/vehicles which deposit in and are released from body fat is of particular value in extending drug availability. The prophylactic action of extended drug residence time, when used with effective grazing/treatment management programmes, provides opportunities for sustainable antiparasitic action. Clearly, with the paucity of new chemical classes of anthelmintics, the use of ‘intelligent’ but still relatively inexpensive carriers/delivery systems for existing actives will form the basis of future parasite control.