Clinical pharmacology in the molecular era.

The title of this article may raise a smile from colleagues in the field of basic pharmacology. To them, pharmacology has always been about molecular interactions, and this title may simply confirm a suspicion that clinical pharmacology is mainly about semi-quantitative observations that have only a limited foundation in hard science. They are partly right, at least regarding a communication problem. In a discussion about systems biology, an exasperated engineer once remarked that biologists and physicians do not even use the same routine software packages that engineers do. Similarly, a basic pharmacologist might note that, whereas he measures drug concentrations in micromoles, the clinical pharmacologist uses micrograms per milliliters. Nevertheless, as clinical pharmacologists seek to make more quantitative observations at the molecular level in living humans, our colleagues in basic pharmacology are delving into cellular signal transduction systems governed by complex protein-protein interactions and regulated by positive and negative feedback loops. In seeking to understand these systems, they face problems that are similar to the challenge of measurement in intact humans.