Administration Studies in Equine Antidoping Research: Designing Scientific Investigations to Effectively Direct Medication Control in Racehorses

Pharmacokinetics is the study of the movement of drug in the body and includes the processes of absorption, distribution, metabolism, and excretion. Pharmacodynamics is the pharmacologic effect of the drug on the body. The pharmacokinetics of a drug determines its pharmacologic effect. Pharmacokinetic studies describe drug concentrations while pharmacodynamics allow for assessment of drug effects. Combined pharmacokinetic/pharmacodynamic studies allow for integration of drug concentrations with pharmacologic effect. Data generated from pharmacokinetic studies can be especially useful in establishing regulatory recommendations, determining appropriate thresholds, screening limits, administrative stand down times, and corresponding detection times. To generate the appropriate information, the following must be considered (1) the test subjects (i.e., number, age, breed, and fitness level), (2) selection of an appropriate dose/route and duration of administration, (3) sample matrix (blood, urine, and hair), (4) time(s) of sample collection, (5) development of an analytical method with appropriate sensitivity, and (6) what analytes to measure (parent and/or metabolite). Pharmacokinetic studies generate drug concentration data that can be used to calculate key pharmacokinetic variables necessary for establishing screening levels and detection times. Pharmacodynamic assessments can aid in understanding the pharmacologic effects of drugs and in correlating drug concentrations to these effects. Various models, including in vivo (whole animal), in vitro, and ex vivo assessments, can be utilized to determine pharmacodynamic effects. Factors to consider in the design of pharmacokinetic studies, basic pharmacokinetic parameters, and examples of pharmacodynamic assessments will be discussed in detail during this tutorial.