Pharmacokinetic/pharmacodynamic approach to assess irrelevant plasma or urine drug concentrations in postcompetition samples for drug control in the horse.

This research paper proposes a method to identify insignificant drug concentrations in horse plasma and urine during post-competition tests, which can help authorities decide whether or not to report nominal traces of therapeutic drugs. The approach combines the principles of pharmacokinetics and pharmacodynamics, and includes calculating the minimal drug withdrawal time to verify the results.

Introduction and Method Proposal

• The authors note that current techniques for controlling drug use in horses often lead to detection of trace levels of drugs, which were legitimately used for therapeutic purposes.
• This study aims to establish a systematic approach that can determine ‘irrelevant’ drug plasma concentrations (IPC) and urine concentrations (IUC).
• This proposed method exploits the principles of pharmacokinetics, the study of how drugs move through the body, and pharmacodynamics, the study of the biochemical and physiological effects of drugs and their mechanisms of action.

Method Execution

• The method starts with using the published plasma clearance rate to convert a typical effective dose of a drug into an effective plasma concentration (EPC).
• Next, a safety factor (SF) is applied to the EPC to derive the IPC. This safety factor seeks to account for any uncertainties or variables not considered within the simpler conversion.
• The entire method rests on certain assumptions, such as the drug effects being reversibly driven by plasma concentration and a linear correlation of drug disposition.
• The suitability and accuracy of the IPC and IUC calculated can be verified by determining the residual drug amount remaining at IPC and calculating a minimum drug withdrawal time.

Conclusion and Implications

• The researchers conclude that monitoring the drug effect (using drug or any analyte concentration as a marker) rather than the mere exposure to the drug could be more rigorous and demanding.
• They also highlight that owing to this, urine might not be the ideal matrix for such testing and analysis.
• This discussion is significant to regulatory authorities as it may influence whether or not trace levels of legitimate therapeutic drugs should be reported in competition horses.