科研之友
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摘要
Until relatively recently, the antiparasitic products available to the veterinarian were often inadequate [1]. During the last two or three decades however, remarkable progress has been achieved in some areas of parasite control through better understanding of the behaviour and lifecycles of the target parasites and the introduction of a new generation of antiparasitics [1,2]. By the end of the last decade of the twentieth century avermectins (for example ivermectin and doramectin) and milbemycins (for example moxidectin), because of their activity against both endoparasites and ectoparasites, had become well established as endectocides for the treatment of livestock. The development of the equivalent products for cats and dogs evolved more slowly, perhaps because companion animals were not the priority for pharmaceutical development initially. The first avermectin-based product approved for use in companion animals was a low-dosage formulation of ivermectin solely for the prevention of adult heartworm (Dirofilaria immitis) infestations in dogs [3]. Higher doses of ivermectin, which might have provided a broader spectrum of activity allowing control of more parasite species, were unattainable because of idiosyncratic toxic reactions in some breeds of dog [4]. Thereafter a systematic programme to evaluate avermectin analogues resulted in the discovery of the macrocyclic lactone selamectin, which was shown to have efficacy and safety profiles which warranted its commercialisation for cats and dogs [5].During the pre-development evaluation of the safety and efficacy of selamectin in dogs and cats, the compound was administered topically and orally at various intervals and dosages and its efficacy against target endo-and ectoparasites was assessed. In studies conducted early in the discovery and development process, selamectin was administered orally in some studies and topically in others. These studies demonstrated conclusively the efficacy of the compound, when appli
