Abstract
Being presented with the WAAVP Pfizer award for excellence in parasitological research is the pinnacle of my career. In accepting I acknowledge the support that I have received from workmates, colleagues, friends and family over the years that I have been involved in this field of endeavour. Parasitic disease is the most significant threat to the Australian sheep industry. A lack of understanding of drug action, the absence of epidemiologically-based treatment programs and incorrect or excessive chemical use has resulted in the development of worm, lice and blowfly parasites which are resistant to most existing chemotherapeutic compounds. During the past decade, difficulties in sustainable control of parasitic disease, the decline in demand for wool products and competition from less expensive synthetic fibre has halved the sheep population and profitability of the industry. Notwithstanding this, a ‘right-sized’, sustainable industry is emerging which will require effective chemotherapy to be the cornerstone of parasite control. Chemical intervention in parasitic disease is therefore here to stay but the paucity of new antiparasitic products in the short term dictates that present therapeutics are all that producers will have for the foreseeable future. This situation will necessitate innovative practices and formulations to provide more cost effective, efficient drug performance and to extend parasiticide life. However, the development of multiple drug resistance and reduction in funds for parasitological research seriously compromises our ability to confront these demands. With the patent life of all but the most recent macrocyclic lactone (ML) compounds lapsing, low cost development of bioequivalent generic formulations and options for innovative strategies to increase performance and market share are eagerly sought. The key to efficient drug use lies in a detailed understanding of the pharmacokinetic principles of drug action and the host animal’s physiological responses to identify procedures which maximise drug availability — in essence giving the drug the best chance to work. It is therefore evident that the how, where and why of drug exchange between the bloodstream and the gastrointestinal tract are of such interest. Of particular importance is identification of the kinetic and dynamic behaviour of drug in the gastrointestinal tract (GIT) and the role of biliary secretion and metabolic fate of biliary (and non-biliary) compounds. The extent to which biliary secreted parent drug and/or metabolites are presented to the gut lumen, reabsorbed as free compound or after deconjugation by large bowel bacteria, and participate in the enterohepatic cycle is a major contributor to parasite exposure. Integrating parasiticide disposition with host physiology, particularly relating to such aspects as gastrointestinal function, feed intake and body condition has demonstrated the value of ‘whole body’ pharmacokinetic studies to identify processes to increase drug efficacy. Novel formulation modifications to provide ‘targeted’ drug delivery including carrier technology, sustained release devices and site-directed formulations can manipulate pharmacokinetic disposition to direct or extend drug availability to the parasite infection. These research directions should be undertaken as collaborative projects between research organisations and the veterinary pharmaceutical industry. With the identification of methods to improve drug action, emphasis must then be directed towards effective communication for their implementation. It will be vital that parasitologists move out of the laboratory to actively disseminate knowledge to the producer. We are ambassadors for our profession and if we fail to communicate well the perception, and indeed the value, of our work can be at risk.
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