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Apparent effect of probenecid on the distribution of penicillins in man
Author(s) -
Milo Gibaldi,
Schwartz Michael A.
Publication year - 1968
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt196893345
Subject(s) - probenecid , distribution (mathematics) , pharmacology , chemistry , volume of distribution , drug , cephaloridine , pharmacokinetics , antibiotics , cephalosporin , medicine , biochemistry , mathematical analysis , mathematics
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.