Pharmacokinetics of probenecid and the effect of oral probenecid administration on the pharmacokinetics of cefazolin in mares.

This research investigates the behavior of probenecid, a medication commonly used to increase uric acid excretion in the body, as it is administered either intravenously or orally in mares. The study also observes the interaction, or lack thereof, between probenecid and cefazolin, an antibiotic, noted to be unaffected by concurrent administration of probenecid.

Probenecid Pharmacokinetics

• In this study, probenecid was administered to mares intravenously and orally at a dosage level of 10 mg per kg of body weight.
• The intravenous administration of probenecid was found to undergo a rapid disposition phase with an average half-life of 14.0 minutes, followed by a slower elimination phase with an average half-life of 87.8 minutes in 5 of the 6 mares. One of the mares did not exhibit a rapid disposition phase, and the half-life of the elimination phase was slower (172 minutes).
• The average residence time of probenecid was reported to be 116 minutes for all mares, with an average of 89.2 minutes specifically for those with a biphasic disposition.
• Average total plasma clearance for probenecid was about 1.18 ml per minute per kg, with renal clearance contributing to roughly 42.6% of the total clearance. The average steady-state volume of distribution for probenecid was about 116 ml per kg.
• The research showed that probenecid is extensively plasma protein bound, with virtually all 99.9% of the medication bound at probenecid concentrations of 10 micrograms per ml.

Oral Administration and Interaction with Cefazolin

• In the case of oral administration, the maximum plasma concentration of probenecid was observed to be about 30 micrograms per ml. The half-life after oral intake was reported to be approximately 120 minutes. The authors found that probenecid demonstrated good oral bioavailability, stating that more than 90% of the administered dose was absorbed.
• The research also included evaluating the potential impact of probenecid on tubular secretion of organic anions, by assessing the pharmacokinetics of intravenous cefazolin alone and then again 15 minutes after oral administration of probenecid.
• The results indicated that concurrent administration of probenecid did not affect the pharmacokinetics of cefazolin. The authors suggest that the reason for this might be due to insufficient plasma concentrations of probenecid following oral administration.