MODELS FOR ASSESSING THE RELATIONSHIP BETWEEN DRUG CONCENTRATION AND DRUG EFFECT IN PERFORMANCE HORSES

The actions of most drugs are dependent upon achieving adequate plasma concentrations. Plasma concentrations are influenced by the degree to which a drug is absorbed, distributed, metabolized and excreted. Phar macokinetic assessment reflects changes in these variables as a functi on of time. Pharmacodynamics refers to specific drug effects or mechan isms of drug action. Individual drug pharmacokinetics provides informa tion on which to base a therapeutic dose, route of administration and dosing interval. However, not all drug actions temporally correlate wi th plasma kinetics. To resolve this discrepancy, pharmacodynamic model s of drug action have been developed. In this review several pharmacod ynamic models of anti-inflammatory and central nervous system effects are discussed in relationship to individual drug pharmacokinetics in t he horse. The use of appropriate statistical models can minimize error and maximize the detection of drug effects over time. Data are presen ted showing the value of pharmacodynamic models in assessing and predi cting the onset, peak and duration of drug action. Penetration of drug s into inflamed tissue or the brain may not temporally correlate with plasma kinetics. Therefore, drug kinetics in tissues or compartments a ssociated with a particular effect may be a better predictor of effica cy than plasma concentrations. Recent studies have shown that exercise can affect drug disposition and influence both pharmacokinetics and p harmacodynamics. In competitive athletes, plasma or urine concentratio ns of drugs are determined to regulate use. Some jurisdictions are adv ocating the establishment of specific drug thresholds based upon plasm a or urine concentrations. However, drug effects may occur during low or undetectable plasma concentrations. Urine concentrations are often dissociated in time from those in plasma. Therefore, the use of approp riate pharmacodynamic models, and the exercising horse, can complement plasma pharmacokinetics in determining drug efficacy and drug thresho lds.