Probenecid combined with penicillin

Combination with probenecid. Renal elimination of penicillin occurs chiefly via the anion (acid)-secretory system of the proximal tubule (-COOH of 6-APA). The acid probenecid (p. 316) competes for this route and thus retards penicillin eUmination ... 

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. 

In those with gout, the serum uric acid level is usually elevated. Sulfinpyrazone increases the excretion of uric acid by the kidneys, which lowers serum uric acid levels and consequently retards the deposit of urate crystals in the joints. Probenecid (Benemid) works in the same manner and may be given alone or with colchicine as combination therapy when there are frequent, recurrent attacks of gout. Probenecid also has been used to prolong the plasma levels of the penicillins and cephalosporins. 

Penicillin + probenecid Threefold increase in serum penicillin level with increase also in spinal fluid levels but decreased brain level Displacement from protein binding, decreased renal tubule secretion and decrease biliary excretion Combination can be used when high serum and spinal fluid levels are required... 

It is possible that drugs that are secreted by the renal tubules (e.g. probenecid, penicillin) could decrease the clearance of pemetrexed, which is also secreted by this mechanism. For this reason, the manufacturer recommends caution with combined use, and, if necessary, close monitoring of creatinine clearance. ... 

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