Probenecid interaction with penicillin

Interference with active transport. Organic acids are passed from the blood into the urine by active transport across the renal tubular epithelium. Penicillin is mostly excreted in this way. Probenecid, an organic acid that competes successfully with penicillin for this transport system, may be used to prolong the action of penicillin when repeated administration is impracticable, e.g. in sexually transmitted diseases, where compliance is notoriously poor. Interference with renal excretion of methotrexate by aspirin, of zidovudine by probenecid and of digoxin by quinidine, contribute to the potentially harmful interactions with these combinations. 

Clinically important, potentially hazardous interactions with acitretin, aldesleukin, aminoglycosides, amiodarone, amoxicillin, ampicillin, aspirin, bacampicillin, bismuth, carbenicillin, chloroquine, cisplatin, cloxacillin, co-trimoxazole, dapsone, demeclocycline, dexamethasone, diclofenac, dicloxacillin, etodolac, etoricoxib, etretinate, fenoprofen, flurbiprofen, folic acid antagonists, haloperidol, hydrocortisone, ibuprofen, indomethacin, influenza vaccines, ketoprofen, ketorolac, lithium, magnesium trisalicylate, meclofenamate, mefenamic acid, methicillin, mezlocillin, minocycline, nabumetone, nafcillin, naproxen, NSAIDs, omeprazole, oxacillin, oxaprozin, oxytetracycline, paromomycin, penicillin G, penicillin V, penicillins, phenylbutazone, piperacillin, piroxicam, polypeptide antibiotics, prednisolone, prednisone, probenecid, procarbazine, rofecoxib, salicylates, salsalate, sapropterin, sulfadiazine, sulfamethoxazole, sulfapyridine, sulfasalazine, sulfisoxazole, sulindac, tazobactum, tenoxicam, tetracycline, ticarcillin, tolmetin, trimethoprim, vaccines... 

Penicillins and Probenecid. A number of organic acids are actively transported from the blood into the tubular urine and vice versa. In some situations, these agents interfere with each other s excretion. Probenecid (e.g., Benemid) can increase the serum concentrations and increase and prolong the activity of penicillin derivatives by blocking their tubular secretion. This is an interaction that has been used to therapeutic advantage in the treatment of certain infections. 

The increased levels and decreased renal excretion of clinafloxacin caused by probenecid are not considered large enough to warrant dosage adjustment," and most of the changes seen with the other quinolones were of a similar magnitude. However, caution has been advised in the presence of other drugs that may also compete for renal excretion (such as some penicillins or cephalosporins). " Grepafloxacin, moxifloxacin, sparfloxacin, and probably ofloxacin, appear not to interact. 

In 1950 (but not reported until 1975) a woman with subacute bacterial endocarditis was given probenecid orally and penicillin by intravenous drip, which was kept open with minimal doses of heparin. After a total of about 20 000 units of heparin had been given over a 3-week period, increasing epistaxes developed and the clotting time was found to be 24 minutes (normal 5 to 6 minutes). This was controlled with protamine. However, no reports of this interaction appear to have been made subsequently. This interaction seems unlikely to be of general significance. 

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