Models for assessing the relationship between drug concentration and drug effect in performance horses.

The research article focuses on understanding how drugs affect performance horses, and how factors such as drug absorption, distribution, metabolism and excretion can alter these effects. The article also highlights the use of pharmacodynamic models to predict and understand these drug interactions more accurately, taking into account factors like exercise and individual horse differences.

Plasma Concentrations and Drug Actions

• The research article begins by explaining that the effects of most drugs are dependent on achieving adequate plasma concentrations, which are influenced by how well a drug is absorbed, distributed, metabolized, and excreted from a being’s body.
• The term pharmacokinetics is used to refer to the changes in these factors over time, while pharmacodynamics refers to the specific drug effects or mechanisms of action.
• Understanding the individual pharmacokinetics of drugs allows for more accurate therapeutical dosing, administration, and interval decisions.
• However, the research acknowledges that not all drug actions correlate with plasma kinetics in a timely manner, leading to the development of pharmacodynamic models to understand this discrepancy better.

Pharmacodynamic Models and Drug Effects

• The researchers discuss the application of some pharmacodynamic models, particularly observing the effects of anti-inflammatory drugs and central nervous system effects in horses.
• The value of these models, according to the data presented, lies in their ability to predict and assess the onset, peak, and duration of drug action.
• In some cases, the penetration of drugs into inflamed tissue or the brain may not accurately correlate with plasma kinetics. This suggests that a better predictor of efficacy may be to consider the drug kinetics in tissues or compartments associated with particular effects, rather than plasma concentrations.

Effect of Exercise and Testing Drug Concentrations

• The article also explores how exercise can affect drug disposition, influencing both their pharmacokinetics and pharmacodynamics.
• For competitive sport horses, monitoring the plasma or urine concentrations of drugs forms part of the regulation process. Some regions advocate for specific drug thresholds based on these plasma or urine concentrations.
• However, the researchers stress that drug effects may still occur even during low or undetectable plasma concentrations. Additionally, urine concentrations are often dissociated in time from those in plasma, creating potential discrepancies in monitoring.
• As a result, the researchers advocate for the use of appropriate pharmacodynamic models, supplemented with exercise aspects, to provide a more comprehensive understanding and determination of drug efficacy and thresholds.