The role of drug delivery in controlling indirect pharmacodynamic responses
was assessed via computer simulations and literature review. Simulations o
f responses related to basic indirect response mechanisms were performed fo
r various drug input rates which allowed the importance of drug delivery ra
te 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 I
C50/SC50. The pharmacodynamics of drugs which elicit indirect pharmacologic
responses such as corticosteroids, diuretics, growth hormone, erythropoiet
in and insulin indicate that sustained drug delivery enhances the therapeut
ic efficiency and pharmacodynamic availability. (C) 2001 Elsevier Science B
.V. All rights reserved.