Effect of probenecid on disposition kinetics of ampicillin in horses.

The study explores how probenecid, a drug usually used to treat gout, affects the rate at which horses metabolize antibiotic ampicillin. The research finds that co-administration of these drugs can lead to slower clearance of ampicillin from the horse’s body, which implies that dosage intervals for ampicillin can potentially be lengthened when used alongside probenecid.

Research Objective

• The main objective of this research is to understand the impact of probenecid on the disposition kinetics of ampicillin in horses. Specifically, it investigates how probenecid affects the absorption, distribution, metabolism, and excretion of ampicillin.

Methodology

• The study involved four horses that were each given two intravenous doses of ampicillin sodium, one dose was given alone and the other was given an hour after providing an oral dose of probenecid.
• The researchers monitored the plasma concentration of probenecid over time, particularly noting its maximum concentration and how long it stayed at levels higher than 15 micrograms/ml.
• They then compared the body clearance rate, elimination half-life and the area under the plasma concentration versus time curve (AUC) of ampicillin with and without the presence of probenecid.

Findings

• The presence of probenecid in the horses’ systems slowed down the clearance of ampicillin, indicating a prolonged availability of the antibiotic in the body. This can be seen in the reduced clearance rate and a longer half-life when compared to the measurements taken when ampicillin was administered alone.
• Moreover, probenecid led to a larger AUC for ampicillin, implying an increase in the total drug exposure over time. This accommodates the potential for an extended dosing interval for the antibiotic.
• In conclusion, the data from this study suggests that when probenecid is used along with ampicillin, the dosing interval for ampicillin can be increased from six-eight hours to 12 hours. This is primarily due to the slower clearance of the antibiotic from the body when probenecid is present.

Implications

• The findings of this research could impact veterinary medicine by potentially allowing for more flexible dosing intervals of antibiotics, such as ampicillin, when they are used in combination with probenecid.