Pharmacokinetics and body fluid and endometrial concentrations of trimethoprim-sulfamethoxazole in mares.

This research studied how the drugs trimethoprim and sulfamethoxazole are distributed and eliminated from the body in female horses. The findings suggest that sufficient levels of the drugs can be achieved in most body fluids and tissues to combat major bacterial infections commonly found in horse populations.

Methodology

• The study involved six healthy adult mares (female horses) each given a single IV injection of trimethoprim (TMP) and sulfamethoxazole (SMZ) at a particular dosage.
• The concentration of each drug was tracked in the horses’ serum over 24 hours, which yielded data on how the drugs are eliminated from the body (elimination rate constant, elimination half-life), how readily they spread through body tissues (apparent volume of distribution), and how quickly the body can remove them (clearance).
• Following this, each mare was given five consecutive oral doses of TMP-SMZ at the same dosage at 12-hour intervals.
• The concentrations of TMP and SMZ were measured in various body fluids and tissues, including serum, synovial fluid, peritoneal fluid, cerebrospinal fluid (CSF), urine, and endometrial tissue.
• Finally, the mean concentrations of TMP and SMZ in the serum were compared after the 1st and the 5th dose to assess any increase in drug levels with repeated dosing.

Findings

• Presented data on the pharmacokinetics of TMP and SMZ in mares, offering insights into how these drugs behave in the body of a horse.
• Notably, by the end of the five-dose regimen, the concentrations of TMP and SMZ in various body fluids and the endometrial tissue (with the exception of the CSF) were high enough to inhibit major bacteria known to cause infections in horses.
• Despite the overall increase in the serum concentrations of TMP and SMZ after five doses, it was only the rise in TMP levels that was statistically significant.
• The absorption of both drugs after oral administration was found to be variable – it differed case by case.

Implications

• The study provides valuable information for veterinary physicians prescribing these drugs, allowing for more effective dosage planning.
• The researchers suggest that this dosage regimen could be effective for treating a range of bacterial infections in horses, given the drugs’ ability to reach inhibitory concentrations in various body fluids and tissues.