Repeated administration of trimethoprim/sulfadiazine in the horse–pharmacokinetics, plasma protein binding and influence on the intestinal microflora.

The research investigated the effects of intravenous and oral administration of trimethoprim/sulfadiazine in horses, exploring its pharmacokinetics, impact on intestinal microflora, plasma levels, and plasma protein binding. Overall, it was found that there were no significant changes to the horses’ bacterial intestinal flora following the administration of the drug, and that oral administration was a satisfactory method for obtaining necessary plasma levels.

Methodology

• Six healthy adult horses were chosen as subjects for this study. The experiment involved repeated administration of the drug combination trimethoprim/sulfadiazine (TMP/SDZ).
• The dose was given twice daily for 5 days, with a 3-week break between intravenous and oral administration. The drug was given intravenously at 2.5 mg/kg TMP and 12.5 mg/kg SDZ concentrations and orally in the form of a paste at 5 mg/kg TMP and 25 mg/kg SDZ concentrations.

Influence on the Intestinal Microflora

• The effect of TMP/SDZ on the horses’ intestinal microflora was investigated. No major changes in the balance of bacteria living in the horse’s intestines were observed, and the horses did not show any clinically observable signs of gastrointestinal disturbances.
• However, a slight reduction in the number of coliform bacteria was noted during the treatment. Interestingly, the route of administration, oral or intravenous, did not seem to cause different effects.

Pharmacokinetics and Plasma Protein Binding

• Various parameters such as the minimum concentration during a dose interval at steady state (Cminss), the elimination half-life (t1/2beta), the mean residence time (MRT), and plasma protein binding were determined and compared between both methods of administration.
• For both TMP and SDZ, the Cminss, t1/2beta, and MRT were significantly greater after oral administration compared to intravenous. This suggests that the drug stays in the system longer after oral administration.
• The plasma protein binding, which is the degree to which drugs attach to proteins within the blood, was found to be at 20% for SDZ and 35% for TMP.

Effectiveness of Oral Administration

• The study concluded that the oral administration of TMP/SDZ in a dose of 30 mg/kg, given twice daily in the form of a paste, appeared to be a satisfactory method for maintaining plasma levels above the minimum inhibitory concentration (MIC) values during the time between doses.
• This finding is essential as achieving satisfactory plasma levels is crucial for drug efficacy, especially when treating bacterial infections.