Pharmacodynamic aspects of modes of drug administration for optimization of drug therapy.

Because of various pharmacodynamic properties, such as the nonlinearity of the concentration-effect relationship, activation of feedback homeostatic mechanisms, induction of pharmacodynamic tolerance, etc., administration of the same dose of drug by different modes is expected to produce different outcomes. This review clarifies the theoretical and practical aspects of the impact of different modes of drug administration on the magnitude of response, and hence on therapy outcomes. It discusses how the interrelationship between the pharmacodynamic properties and the drug input function affects the magnitude of response. To demonstrate this special dimension of drug therapy, relevant pharmacodynamic data was obtained for drugs with different therapeutic applications, including antibiotics, analgesics, diuretics, anti-cancer, anti-ulcer, anti-inflammatory, anti-hypertensive, lipid-lowering anti-parkinsonian, and immunosuppressive drugs. These examples provide guidelines for implementing the role of the mode of drug administration (including rate, schedule, and route of drug treatment) during drug development or optimization of drug therapy.