IMPACT OF PHARMACODYNAMIC VARIABILITY ON DRUG-DELIVERY

Modern pharmaceutical delivery systems are intended to produce plasma drug concentration versus time profiles that result in optimum therape utic efficacy and a minimum of drug concentration-dependent adverse ef fects. To accomplish this requires that the drug delivery rate and tem poral profile be based on the pharmacokinetic and pharmacodynamic char acteristics of the specific medicinal agent. Pharmacokinetic and pharm acodynamic parameters are subject to considerable interindividual vari ability. Whereas the importance of pharmacokinetic variability is gene rally recognized, the significance of pharmacodynamic variability (i.e ., variability in the relationship between effect intensity and drug c oncentration) is not as widely appreciated. Pharmacodynamic variabilit y is typically quite large, reproducible, and often substantially exce eds the relative magnitude of pharmacokinetic variability. This articl e consists of a review of how to assess pharmacodynamic variability, c linical examples of pharmacodynamic variability of drugs with a wide r ange of indications, and an outline of mechanisms of pharmacodynamic v ariability. (C) 1998 Elsevier Science B.V. All rights reserved.