Physiologic indirect response models characterize diverse types of pharmacodynamic effects

Abstract

A family of four basic physiologic indirect response models has been proposed to account for the pharmacodynamics of drugs that act by way of inhibition or stimulation of the production or loss of endogenous substances or mediators. Such models were applied previously to account for the anticoagulant effects of warfarin, adrenal suppression by corticosteroids, cell trafficking effects of corticosteroids, antipyretic effects of ibuprofen, and aldose reductase inhibition. Additional responses that can be readily characterized with such models include muscular contraction from pyridostigmine, diuresis from furosemide, bronchodilation from terbutaline, prolactin secretion after cimetidine, and potassium suppression by terbutaline. This report shows that indirect response models, rather than "link" or "hypothetical effect compartment" models, may be more appropriate for diverse drugs when time lags exist between plasma or biophase drug concentrations and the time course of pharmacodynamic responses.