Phenylbutazone Benzylpenicillin

Benzylpenicillin disappears from the blood very rapidly (the elimination half-life is 30 minute in the adult), and 60-90% of dose is excreted in the urine (350). The renal clearance is approximately equal to the blood flow rate, indicating a high secretion clearance (350). Probenecid and phenylbutazone reduced its renal clearance to 60%, while sulfinpyrazone reduced it to 40% of the control value (351). In rat kidney, Oat3 has been suggested to be responsible for the uptake of benzylpenicillin (53). As discussed above, inhibition of uptake process mediated by OAT3 is likely mechanics underlying this interaction. 

Osmotic diuretic mannitol Aminoglycosides Organic anions p-Aminohippurate or benzylpenicilline Phenobarbital Phenylbutazone Oxipurinol Organic cations ... 

Aspirin, indometacin, phenylbutazone, sulfaphenazole and sulfinpyrazone prolong the half-Ufe of benzylpenicillin whereas chlorothiazide, sulfamethizole and sulfamethoxypyridazine do not. Some sulfonamides reduce oxacillin blood levels. Pirenzepine does not affect the pharmacokinetics of amoxicillin. 

Studies in patients given different drugs for 5 to 7 days showed the following inereases in the half-life of benzylpenicillin aspirin 63%, indometacin 22%, phenylbutazone 139%, sulfaphenazole 44% and sulfinpyrazone 65%. It seems likely that competition between these drugs and benzylpenicillin for excretion by the kidney tubules caused these increases. Changes in the half-life with chlorothiazide, sulfamethizole and sulfamethoxypyridazine were not significant. ... 

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