Plasma and urine pharmacokinetics of hydroxyzine and cetirizine following repeated oral administrations to exercised horses.

This study examined how the antihistamine drugs hydroxyzine and cetirizine metabolize in horses, providing data on drug detection times which could be used in the regulation of these medications in horse racing.

Purpose and Method of Research

• The research aimed at providing information on the pharmacokinetics (the movement of drugs within the body) of hydroxyzine and cetirizine in horses. Specifically, these substances were administered to a group of thoroughbred horses and their levels in the plasma and urine were monitored over time.
• It is important to note, hydroxyzine is a first-generation antihistamine, and cetirizine, which is a second-generation antihistamine, is also a metabolite of hydroxyzine, adding an extra level of complexity to determining their presence and quantities in the body.
• The study involved giving 9 repeated doses of hydroxyzine HCl (500 mg) to six horses and cetirizine HCl (190 mg) to two horses. Levels of these drugs in both plasma and urine were then measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Algorithm Development and Analysis

• A non-linear mixed effects pharmacokinetic model was developed, which accounted for the concentrations of hydroxyzine and cetirizine in plasma and urine, either when administered separately or when cetirizine was produced as a metabolite of hydroxyzine.
• The study used this model, in conjunction with methodology established by Toutain, to suggest possible screening limits (SL). These limits could determine a detection time (DT) of up to 4 days for either drugs in the plasma or urine of horses.

Predictive Analysis and Conclusion

• The researchers also used their model to calculate hydroxyzine and cetirizine concentration prediction intervals for the 80th, 95th and 99th percentiles of a ‘virtual’ horse population – an analysis designed to assess the accuracy and reliability of the proposed DT.
• Despite their detailed analysis, the study acknowledges that the responsibility for determining the threshold risk levels for these drugs ultimately lies with individual racing authorities.