Translational Research: Preclinical to Healthy Volunteer to Patient

The development of medicines involves not only the translation of information collected in preclinical in vitro and in vivo experiments to clinical studies in healthy volunteers, also known as T1 translation, but additionally the optimization of the new medication within the environment of medical care, the translation from healthy volunteer to patient, also known as T2 translation. How do the pharmacokinetic parameters vary with different doses? What is the best dose? Can the new medication be combined with other therapies? This chapter begins with a discussion of the overall strategy and individual steps to determine a drug candidate’s pharmacology, absorption, distribution, metabolism, and elimination (ADME), and drug-drug interactions in clinical studies, as well as subsequent evaluation of preclinical predictions. Integration of concentration-time data to develop population pharmacokinetic models and the use of biomarkers in clinical studies are discussed. Biomarkers can be particularly helpful in diseases where obvious clinical pathology may lag behind changes in laboratory values or other more easily measured surrogates. Case studies are also presented illustrating applications of translational research in the development of possible therapeutic agents for the treatment of osteoporosis and Alzheimer’s disease.