Role of dosage regimen in controlling indirect pharmacodynamic responses

The role of drug delivery in controlling indirect pharmacodynamic responses was assessed via computer simulations and literature review. Simulations of responses related to basic indirect response mechanisms were performed for various drug input rates which allowed the importance of drug delivery rate on the overall pharmacodynamic response to be evaluated. Response versus time profiles of integrated or net responses and efficiency were examined. Rate of drug input has the greatest influence on the area under the effect curve when doses are larger and target drug concentrations are above the IC50/SC50. The pharmacodynamics of drugs which elicit indirect pharmacologic responses such as corticosteroids, diuretics, growth hormone, erythropoietin and insulin indicate that sustained drug delivery enhances the therapeutic efficiency and pharmacodynamic availability. (C) 1998 Elsevier Science B.V. All rights reserved.