A clinician's guide to factors affecting withdrawal times for equine therapeutic medications

Equine forensic science can now detect concentrations down to 25 femtograms/mL (parts per quadrillion, ppq) or less in blood and urine. As such, horsemen are increasingly at risk of inadvertent 'positives' due to therapeutic medication 'overages' or trace identifications of dietary or environmental substances. Reviewed here are the factors which determine detection times and 'withdrawal times' for substances administered to horses. Withdrawal times are affected by many factors, including dose, formulation, route and frequency of administration, bioavailability, plasma half-life, sensitivity of the analytical process, the testing matrix (plasma, urine, or other), and the environmental presence and/or persistence of administered substances. Of these factors only dose is known precisely. For any given administration, horse-to-horse differences in the volumes of distribution, systemic clearance, and terminal plasma elimination half-life of substances are major and totally uncontrollable factors driving horse-to-horse variability in withdrawal times. A further complication is that chemically stable medications administered to horses and eliminated in the urine inevitably become part of the environment of the horse. The presence of these substances in the equine environment is increasingly giving rise to trace identifications long after nominal administration of these substances has ceased. Because of the unknown and uncontrollable horse-to-horse variability in medication pharmacokinetics, any therapeutic medication administration to a horse by definition includes the possibility of an inadvertent medication overage. As such, the caveat that there are no guarantees in life most assuredly applies to advisories concerning equine therapeutic medication withdrawal times.