Effects of a single dose of orally and rectally administered misoprostol in an in vivo endotoxemia model in healthy adult horses.

This research aims to understand how administering misoprostol, a medication, orally or rectally affects its pharmacokinetics (how the drug behaves in the body) and anti-inflammatory properties in horses when they are subjected to an endotoxin challenge.

Methods

• The study involved six healthy geldings (castrated male horses).
• A randomized three-treatment crossover design was used with a gap of at least 28 days between different treatment groups.
• Before the horses were introduced to an endotoxin (lipopolysaccharide administered at a dose of 30 ng/kg IV over 30 minutes), they were administered a single dose of misoprostol (5 µg/kg) either orally (M-PO) or rectally (M-PR) or were given water as a control (CON).
• The researchers monitored clinical parameters and took blood samples to measure different markers: plasma concentration of misoprostol free acid, count of white blood cells (leukocytes), and gene expression and serum concentrations of pro-inflammatory compounds tumor necrosis factor-alpha (TNFα) and interleukin 6 (IL-6).

Results

• The study found that in the M-PO group, the maximum plasma concentration and total drug exposure (as measured by the area under the concentration versus time curve) were higher compared to those in the M-PR group.
• The time taken to reach maximum concentration in the blood was also longer in the M-PO group compared to the M-PR group.
• However, no significant differences were found in clinical parameters, leukocyte counts, and TNFα or IL-6 gene expression or serum protein concentration among the different treatment groups.
• Although there was some downregulation (decrease) in relative gene expression in individual horses in both the M-PO and M-PR groups at select times.

Conclusions

• The study concluded that there was significant variability among horses within and between treatment groups in terms of the measures taken.
• The absorption and systemic exposure of misoprostol following oral administration differed from previous reports in horses not administered LPS.
• The researchers, therefore, proposed further investigation with multiple doses of misoprostol to better evaluate its effectiveness as an anti-inflammatory therapy.