Clinical pharmacokinetics

Clinical pharmacokinetics of probenecid.

PMID 7011657


A review of the clinical applications and of the disposition of probenecid in man, including drug interactions, is presented. Probenecid is the classical competitive inhibitor of organic acid transport in the kidney and other organs. There are 2 primary clinical uses for probenecid: as a uricosuric agent in the treatment of chronic gout and as an adjunct to enhance blood levels of antibiotics (such as penicillins and cephalosporins). Adsorption of probenecid is essentially complete following oral administration. The drug is extensively metabolised by glucuronide conjugation and by oxidation of the alkyl side chains; oxidation of the aromatic ring does not occur. The half-life of probenecid in plasma (4 to 12 hours) is dose-dependent. Renal excretion is the major route of elimination of the metabolites; excretion of the parent drug is minimal and is dependent on urinary pH. Probenecid and its oxidised metabolites are extensively bound to plasma proteins, mainly to albumin. Tissue concentrations (based on animal studies) are generally lower than plasma concentrations. Most of the drug-drug interactions involving probenecid are due to an effect on the kidney-block of transport of acidic drugs. Similarly probenecid affects the tubular secretion of a number of acidic endogenous substances by the kidney. Probenecid is also involved in the block of transport of acidic metabolites of catecholamines, for example homovanillic and hydroxyindoleacetic acids, in the brain. There are a number of analytical procedures for the assay of probenecid. These are based on spectrophotometry, spectrofluorometry, gas and liquid chromatography and radioimmunoassay.