Cetirizine in horses: pharmacokinetics and effect of ivermectin pretreatment.

The research investigates how the drug cetirizine, an antihistamine, behaves in the body of horses and the extent to which a preceding dose of the antiparasitic drug ivermectin can affect this behaviour.

Pharmacokinetics of Cetirizine

The researchers conducted a careful examination of how cetirizine moves through and interacts with the body of horses. Specifically, they observed its absorption, distribution, metabolism, and excretion processes. Key findings included:

• The drug’s terminal half-life, or the time it takes to eliminate half of the drug from the body, was 3.4 hours on average. This range varied from 2.9 to 3.7 hours.
• The highest concentration of cetirizine in the blood plasma reached was 132 ng/mL on average.
• The time taken to reach the peak plasma concentration was on average 0.7 hours.

Effects of Ivermectin Pretreatment

The research also focused on observing the effects of administering ivermectin, an antiparasitic drug, before giving cetirizine and determined that:

• Ivermectin, when given 1.5 hours prior to cetirizine does not have any noticeable impact on cetirizine’s pharmacokinetics.
• However, administering ivermectin 12 hours before cetirizine led to a 60% increase in the area under the plasma concentration-time curve (AUC). This means cetirizine spent a longer time in the body at effective concentrations.
• After a 12 hour pretreatment, the maximum plasma concentration, terminal half-life, and mean residence time (average time a molecule stays in the body) also showed a significant increase.

Potential Mechanism of Interaction

The researchers concluded that this increase could be due to ivermectin’s inhibitory effect on P-glycoprotein, a protein involved in transporting drugs out of cells. This inhibition could lead to decreased renal secretion and thereby increased plasma levels of cetirizine. This is because P-glycoprotein is located in the proximal tubular cells of the kidney, which play a significant role in eliminating drugs from the body.

Implications

According to the findings, cetirizine possesses properties that make it a potential antihistamine drug for use in horses. Moreover, the results suggest that the administration of ivermectin prior to cetirizine can enhance the drug circulating levels and its residency in the body. This may have practical implications for enhancing the drug efficacy in horses when treating allergic reactions. However, it’s important to consider the timing of the ivermectin administration for optimal impact.