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. 1974 Sep;6(3):300–303. doi: 10.1128/aac.6.3.300

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

Ernst H Nauta 1, Herman Mattie 1, Wim R O Goslings 1
PMCID: PMC444640  PMID: 15830476

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. DAYTON P. G., YU T. F., CHEN W., BERGER L., WEST L. A., GUTMAN A. B. The physiological disposition of probenecid, including renal clearance, in man, studied by an improved method for its estimation in biological material. J Pharmacol Exp Ther. 1963 Jun;140:278–286. [PubMed] [Google Scholar]
  2. Fishman R. A. Blood-brain and CSF barriers to penicillin and related organic acids. Arch Neurol. 1966 Aug;15(2):113–124. doi: 10.1001/archneur.1966.00470140003001. [DOI] [PubMed] [Google Scholar]
  3. Gibaldi M., Davidson D., Plaut M. E., Schwartz M. A. Modification of penicillin distribution and elimination by probenecid. Int Z Klin Pharmakol Ther Toxikol. 1970 May;3(2):182–189. [PubMed] [Google Scholar]
  4. Gibaldi M., Schwartz M. A. Apparent effect of probenecid on the distribution of penicillins in man. Clin Pharmacol Ther. 1968 May-Jun;9(3):345–349. doi: 10.1002/cpt196893345. [DOI] [PubMed] [Google Scholar]
  5. Kenwright S., Levi A. J. Impairment of hepatic uptake of rifamycin antibiotics by probenecid, and its therapeutic implications. Lancet. 1973 Dec 22;2(7843):1401–1405. doi: 10.1016/s0140-6736(73)92799-2. [DOI] [PubMed] [Google Scholar]
  6. Mattie H., Goslings W. R., Noach E. L. Cloxacillin and nafcillin: serum binding and its relationship to antibacterial effect in mice. J Infect Dis. 1973 Aug;128(2):170–177. doi: 10.1093/infdis/128.2.170. [DOI] [PubMed] [Google Scholar]
  7. Nauta E. H., Mattie H., Goslings W. R. Pharmacokinetics of cloxacillin in patients on chronic intermittent haemodialysis and in healthy subjects. Chemotherapy. 1973;19(5):261–271. doi: 10.1159/000221464. [DOI] [PubMed] [Google Scholar]
  8. WAGNER J. G., NELSON E. KINETIC ANALYSIS OF BLOOD LEVELS AND URINARY EXCRETION IN THE ABSORPTIVE PHASE AFTER SINGLE DOSES OF DRUG. J Pharm Sci. 1964 Nov;53:1392–1403. doi: 10.1002/jps.2600531126. [DOI] [PubMed] [Google Scholar]
  9. WEINER I. M., WASHINGTON J. A., 2nd, MUDGE G. H. On the mechanism of action of probenecid on renal tubular secretion. Bull Johns Hopkins Hosp. 1960 Jun;106:333–346. [PubMed] [Google Scholar]

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