Apparent effect of probenecid on the distribution of penicillins in man

Pharmacokinetic analysis of literature data on drug serum levels after administration of ampicillin, ancillin, nafcillin, and cephaloridine, with and without probenecid, suggests a new mechanism of action of probenecid. The results indicate that while probenecid markedly diminishes tubular secretion of the drugs, this effect is not the principal one in accounting for the enhanced serum levels of drug. More important, is the fact that a significant decrease in the apparent volume of distribution of each drug in the presence of probenecid has been observed. The decrease in distribution volume results in a larger fraction of drug in the body in the central compartment and gives rise to higher serum levels. A number of possible effects of probenecid aTe explored to explain the observed phenomenon.