Abstract
Receptor occupancy is an important indicator for drug efficacy. Traditional pharmacodynamic model is constrained by assumption of rapid equilibrium, so it cannot provide a complete picture of drug action. Pulsed drug delivery is not aimed at the stability of the drug, but at accurately determining the time of dosing based on rhythm of onset. Using a minimal model, I found that the Hill-Langmuir equation which removes above assumption, can integrate pharmacokinetics and pharmacodynamics and can describe receptor occupancy under multiple dose regimens and pulsed drug delivery. This equation provides an optimization strategy for improving drug efficacy. For the traditional multiple dose regimen, we can optimize the elimination rate constant, association rate constant and drug-target residence time; however, for pulsed drug delivery, we can only optimize the drug-target residence time. Furthermore, using the dissociation rate constant, we are not only able to regulate binding affinity, but also control the stability of drug-target binding. And I provided two conditions must be followed in pulsed drug delivery design. These two conditions are the cost in reducing the stability of drug concentration. These results may reduce the failure rate of drug discovery.