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Effect of Probenecid on the Apparent Volume of Distribution and Elimination of Cloxacillin

According to Gibaldi et al. (1968, 1970), the higher serum concentrations of penicillins and cephaloridine reached after administration of probenecid are due not only to slower renal elimination but also to an altered distribution in the body. To determine whether probenecid has a direct effect on the distribution of cloxacillin, the elimination and distribution of cloxacillin was studied in six patients, five lacking kidney function and one with a partially impaired renal function, in the presence or absence of probenecid. No significant difference was found between the mean values of the volume of distribution of cloxacillin with and without probenecid (13.0 and 12.6 liters, respectively). Thus, the hypothesis of Gibaldi et al. could not be confirmed for cloxacillin in patients lacking kidney function. In spite of the absence of kidney function, the value of the elimination rate constant was significantly decreased in the presence of probenecid (from 0.326 to 0.263/h). This might be explained by a blockade by probenecid of the elimination of cloxacillin by the liver.