Should Probenecid be Used to Reduce the Dicloxacillin Dosage in Orthopaedic Infections? A Study of the Dicloxacillin‐Saving Effect of Probenecid

Abstract

Reduction in the dosage of dicloxacillin from 500 mg to 250 mg 3 times a day would mean lowering of costs and less side-effects in orthopaedic infections. In this cross-over study, the serum concentrations of dicloxacillin were measured in 9 patients after administration of dicloxacillin 500 mg 3 times a day (dicloxacillin 500 mg) and after co-administration of 250 mg dicloxacillin and 250 mg probenecid 3 times per day (dicloxacillin 250 mg+probenecid 250 mg). Concentrations were measured every hour after the tablet intake. The mean maximum serum concentrations of dicloxacillin were 17.1 micrograms/ml (dicloxacillin 500 mg) and 12.2 micrograms/ml (dicloxacillin 250 mg+probenecid 250 mg), respectively (P < 0.05). Serum concentrations above 3 micrograms/ml were obtained during 285 min. in both regimes, but the individual variations were biggest during in the dicloxacillin 250 mg+probenecid 250 mg treatment. Serum concentrations above 5 micrograms/ml were in mean measured during 228 min. (dicloxacillin 500 mg) and 190 min. (dicloxacillin 250 mg+probenecid 250 mg), respectively (P < 0.05). The clinical significance of these findings is being discussed. In theory, treatment with dicloxacillin 250 mg+probenecid 250 mg may be as sufficient as dicloxacillin 500 mg.

Probenecid Inhibits Platelet Responses to Aggregating Agents in Vitro and Has a Synergistic Inhibitory Effect with Penicillin G

“…Probenecid is an anion channel blocker (1) and uricosuric agent originally developed to slow the rate of excretion of penicillin (2). It is now in use in combination with a number of other antibiotics and pharmacological agents to reduce their required dosages (3)(4)(5). In several types of cells, probenecid has been used to prevent the leakage of the calcium indicator, fura-2, since this leakage reduces the accuracy of measurements of intracellular calcium concentration ([Ca2+]j) (6)(7)(8)(9).…”

“…Since probenecid is a frequently administered drug (2)(3)(4)(5), and there is some confusion in the literature concerning its mode of action, we have investigated its effects on the responses of platelets to several aggregating and release-inducing agents, including the thrombin receptor-activating peptide SFLLRN, also known as TRAP. In addition, we have explored the combined inhibitory effects of probenecid and penicillin G.…”

Pharmacokinetics and Tolerability of Oseltamivir Combined with Probenecid

“…It inhibits renal tubular urate resorption and has been found to decrease the levels of excretion of several medications, probably through inhibition of organic ion transporter 1 in renal tubular cells. Several studies have been published indicating that probenecid given one to three times daily at doses ranging from 250 to 1,000 mg can result in significant increases in the plasma concentrations of other approved medications (7,15,17,22,23). Probenecid demonstrates dose-dependent pharmacokinetics and nonlinear elimination (10,35).…”

PKQuest: capillary permeability limitation and plasma protein binding – application to human inulin, dicloxacillin and ceftriaxone pharmacokinetics

“…This means that dicloxacillin has the same volume of distributions in the different organs as was used above for inulin. Dicloxacillin is cleared primarily by the kidney in these subjects [12] and there is a large component of renal tubular secretion that is blocked by probenecid [18] determined by the parameter Tclr [kidney]. (Other studies have indicated that the liver can account for 40% or more of the total clearance [16].…”