MODIFYING THE FORMULATION OR DELIVERY MECHANISM TO INCREASE THE ACTIVITY OF ANTHELMINTIC COMPOUNDS

The development of resistance to current chemical classes of broad-spe ctrum anthelmintics poses an undeniable threat to the long-term viabil ity of the animal health industry. Alternative treatment strategies in cluding vaccines, biological control and breeding of parasite-resistan t animals are unlikely to be widely available in the near future and e ven then, they will be integrated with chemotherapy. To compound the s everity of the situation there appears to be no new chemical class of anthelmintics, with unique mode of action, on the horizon. The signifi cant 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/medic al and cosmetic products, provide little incentive for anthelmintic de velopment. The chemical actives that are currently available, are all that we are likely to have for the foreseeable future. If effective pa rasite treatment is to continue, existing actives must be used more ef ficiently. Recognising the potential for the animal's physiological be haviour to assist drug action is of significant value. Reduction of fe ed intake before oral, anthelmintic treatment slows ruminant digesta f low, prolongs and extends the availability and therefore increases eff icacy, of the benzimidazole and ivermectin compounds. This is a cost e ffective option that can be employed which not only increases efficacy of 'older' compounds, but will be instrumental in prolonging the usef ul life of the 'newer' drugs. In a related approach the co-administrat ion of metabolic inhibitors can prolong drug clearance and extend avai lability and increase the action of existing anthelmintics. However, g iven the large costs which would be associated with this development ( host toxicity, residue safety) it is probable that the value of such c ombinations would be more appropriate for use in the treatment of non- food producing animals. The most promising approach for improved formu lation lies in innovative delivery systems using chemical or physical carriers. Solubility-defining salts, oils, solid/drug matrices, liposo mes and related microparticles that reduce drug absorption/metabolism and can specifically direct large quantities of active, over an extend ed or pre-determined period, to the site(s) of parasitic infection. Th e 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 wit h effective grazing/treatment management programmes, provides opportun ities 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 a ctives will form the basis of future parasite control. (C) 1997 Elsevi er Science B.V.