ABSTRACT
Pharmaceutical industry is faced with more challenges than ever in recent years. The drug industry continues to consolidate and become more competitive. Highly publicized lawsuits have heightened sensitivities with respect to the balance between acceptable efficacy and safety. Pharmacodynamics describes the time course and the magnitude of pharmacological response of drugs. Based on the classic receptor-occupancy theory, after drug molecules reach the target biophase, it binds to the receptors to form the drug-receptor complex to exert pharmacological response. An important assumption associated with the simple direct effect models is that a rapid equilibrium exists between plasma and effect site concentrations. Accordingly, maximum effects are predicted to occur simultaneously with peak drug concentrations. Aside from the distribution process, temporal dissociation between the time courses of concentration and effect might also be caused by an indirect response mechanism. The development of tolerance can have a significant impact on the exposure response relationship and, if not recognized, can contribute to poor clinical outcome.
