Jeffrey D. Alder Pages 143 - 158 ( 16 )
Animal models of infection are the most predictive preclinical test for projecting clinical success of experimental antibacterial therapeutics. The first screen for antibacterial drug efficacy is usually prevention of mortality in animal models of infection. Secondary trials for drug efficacy measure the reduction of bacterial burden in defined body sites such as lung, kidney, and soft tissue. These trials determine potential clinical indications for the experimental compounds. Promising compounds are then advanced for additional testing in animal models to identify the key pharmacodynamic parameter predictive of efficacy. The value of the pharmacodynamic parameter that yields efficacy is then numerically defined and related to the blood concentration of experimental drug needed for clinical efficacy. Animal trials to determine appropriate length of therapy are conducted at optimal pharmacodynamic values. Efficacy against relevant drug resistant bacteria should also be determined prior to clinical development. Preliminary toxicity studies are conducted during efficacy testing and safety margins should be known prior to bulk synthesis of drug for formal toxicity studies. At all stages of testing, appropriate clinical antibacterial drugs are used as positive controls. Proper use of animal models will keep the drug development pipeline clear of compounds with little probability of clinical efficacy. This testing program will cause. the selection of experimental anti-bacterial compounds with significant promise for rapid advancement through clinical trials to medical and commercial success.