28 – The Use of Animals in the Search for Anti-inflammatory Drugs

This chapter reviews the recent changes in the way in which pharmacological testing of potential new anti-inflammatory agents is conducted, using representative examples of mechanism-based approaches. These approaches are still experimental for the most part because they have not been clinically proven. The emphasis of in vivo studies in these examples is on demonstrating pharmacological/biochemical efficacy in a facile model at an early stage of drug discovery. This application of in vivo models complements the mechanism-based approach to drug design currently in vogue within the pharmaceutical industry. Once a reasonable level of potency is reached, the activity in a whole animal is determined using assays which do not attempt to model human disease but specifically evaluate the pharmacodynamics of the compound against the pharmacological target of interest. The criteria for taking a compound forward for testing in man are changing from a situation in which activity in an animal model of disease is paramount, to the one where inhibition of a defined mechanism, which is believed to be important in human disease, is the major objective. Valuable information on potential mechanisms that may lead to disease can be obtained from animal studies as similar studies in man may be impossible to perform.