Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1979 Nov;8(5):491–495. doi: 10.1111/j.1365-2125.1979.tb01032.x

Probenecid: an unexplained effect on cephalosporin pharmacology.

P G Welling, S Dean, A Selen, M J Kendall, R Wise
PMCID: PMC1429805  PMID: 508557

Abstract

1 The influence of probenecid on serum levels and urinary excretion of orally administered cephradine and cefaclor has been investigated. 2 Probenecid caused serum levels of both antibiotics to be increased and also prolonged. Urinary excretion of antibiotic activity was slightly but not significantly decreased by probenecid during the initial 6 h postdosing. It was significantly increased in 6-12 h urine, but only a small percentage of the doses were excreted during that period. 3 The increased serum levels of antibiotic were greater than could be accounted for by reduced elimination rate alone. Possible mechanisms to account for increased circulating levels of antibiotic in the presence of probenecid are discussed in the light of previous observations on probenecid induced changes in tissue distribution of beta-lactam antibiotics.

Full text

PDF
491

Selected References

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

  1. Barza M., Brusch J., Bergeron M. G., Weinstein L. Penetration of antibiotics into fibrin loci in vivo. 3. Intermittent vs. continuous infusion and the effect of probenecid. J Infect Dis. 1974 Jan;129(1):73–78. doi: 10.1093/infdis/129.1.73. [DOI] [PubMed] [Google Scholar]
  2. Bint A. J., Reeves D. S., Holt H. A. Effect of probenecid on serum cefoxitin concentrations. J Antimicrob Chemother. 1977 Nov;3(6):627–628. doi: 10.1093/jac/3.6.627-a. [DOI] [PubMed] [Google Scholar]
  3. Craig W. A., Welling P. G. Protein binding of antimicrobials: clinical pharmacokinetic and therapeutic implications. Clin Pharmacokinet. 1977 Jul-Aug;2(4):252–268. doi: 10.2165/00003088-197702040-00002. [DOI] [PubMed] [Google Scholar]
  4. Fishman R. A. Active transport and the blood-brain barrier to penicillin and related orgnic acids. Trans Am Neurol Assoc. 1964;89:51–55. [PubMed] [Google Scholar]
  5. 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]
  6. Foglesong M. A., Lamb J. W., Dietz J. V. Stability and blood level determinations of cefaclor, a new oral cephalosporin antibiotic. Antimicrob Agents Chemother. 1978 Jan;13(1):49–52. doi: 10.1128/aac.13.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. GOETZEE A. E., RICHARDS T. G., TINDALL V. R. Experimental changes in liver function induced by probenecid. Clin Sci. 1960 Feb;19:63–78. [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Glynne A., Goulbourn R. A., Ryden R. A human pharmacology study of cefaclor. J Antimicrob Chemother. 1978 Jul;4(4):343–348. doi: 10.1093/jac/4.4.343. [DOI] [PubMed] [Google Scholar]
  11. Griffith R. S., Black H. R., Brier G. L., Wolny J. D. Effect of probenecid on the blood levels and urinary excretion of cefamandole. Antimicrob Agents Chemother. 1977 May;11(5):809–812. doi: 10.1128/aac.11.5.809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kunst M. W., Mattie H. Probenecid and the antibacterial activity of cephradine in vivo. J Infect Dis. 1978 Jun;137(6):830–834. doi: 10.1093/infdis/137.6.830. [DOI] [PubMed] [Google Scholar]
  13. Mischler T. W., Sugerman A. A., Willard D. A., Brannick L. J., Neiss E. S. Influence of probenecid and food on the bioavailability of cephradine in normal male subjects. J Clin Pharmacol. 1974 Nov-Dec;14(11-12):604–611. doi: 10.1002/j.1552-4604.1974.tb01380.x. [DOI] [PubMed] [Google Scholar]
  14. Nauta E. H., Mattie H., Goslings W. R. Effect of probenecid on the apparent volume of distribution and elimination of cloxacillin. Antimicrob Agents Chemother. 1974 Sep;6(3):300–303. doi: 10.1128/aac.6.3.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Neiss E. S. Cephradine--a summary of preclinical studies and clinical pharmacology. J Ir Med Assoc. 1973 Mar 24;Suppl:1–12. [PubMed] [Google Scholar]
  16. Peterson L. R., Hall W. H., Zinneman H. H., Gerding D. N. Standardization of a preparative ultracentrifuge method for quantitative determination or protein binding of seven antibiotics. J Infect Dis. 1977 Dec;136(6):778–783. doi: 10.1093/infdis/136.6.778. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES