Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1982 Jun;21(6):873–880. doi: 10.1128/aac.21.6.873

Effect of method of administration on extravascular penetration of four antibiotics.

L L Van Etta, G R Kravitz, T E Russ, C E Fasching, D N Gerding, L R Peterson
PMCID: PMC182038  PMID: 7114835

Abstract

The effect of both method of drug administration and serum protein binding on antibiotic penetration into subcutaneous Visking chambers was studied in rabbits. Ampicillin and oxacillin were administered by either repeated intramuscular injection of 30 mg/kg every 4 h or by constant infusion of 7.5 mg/kg per h for 24 h. Gentamicin was given by intramuscular injection of 4 mg/kg every 4 h for 28 h and by constant infusion of 1 mg/kg per h for 24 h. Amikacin was given by intramuscular injection of 8 mg/kg every 4 h for 12 h and by constant intravenous infusion of 2 mg/kg per h for 12 h. Protein binding to rabbit serum was 73% for oxacillin, 9% for ampicillin, 19% for gentamicin, and 0% for amikacin. Chamber concentrations achieved for oxacillin, gentamicin, and amikacin were not significantly different for constant infusion versus intermittent administration. For ampicillin, chamber concentration was slightly higher by constant infusion than by intermittent administration (P less than 0.02). Fluctuations in drug concentration from peak to trough values in the chambers during the intermittent administration studies were markedly dampened when compared with serum fluctuations. This study demonstrates that whereas steady state is reached more rapidly by intermittent administration, the mean steady-state concentration of an antibiotic achieved at an extravascular site is the same or greater by constant infusion than by intermittent dosing. This is true for highly protein bound antibiotics as well as those with low serum protein binding.

Full text

PDF
873

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. Bergan T. Pharmacokinetics of tissue penetration of antibiotics. Rev Infect Dis. 1981 Jan-Feb;3(1):45–66. doi: 10.1093/clinids/3.1.45. [DOI] [PubMed] [Google Scholar]
  3. Bergeron M. G., Beauchamp D., Poirier A., Bastille A. Continuous vs. intermittent administration of antimicrobial agents: tissue penetration and efficacy in vivo. Rev Infect Dis. 1981 Jan-Feb;3(1):84–97. doi: 10.1093/clinids/3.1.84. [DOI] [PubMed] [Google Scholar]
  4. Ehrlich H. P., Licko V., Hunt T. K. Kinetics of cephaloridine in experimental wounds. Am J Med Sci. 1973 Jan;265(1):33–44. doi: 10.1097/00000441-197301000-00003. [DOI] [PubMed] [Google Scholar]
  5. Gerding D. N., Hall W. H., Schierl E. A. Antibiotic concentrations in ascitic fluid of patients with ascites and bacterial peritonitis. Ann Intern Med. 1977 Jun;86(6):708–713. doi: 10.7326/0003-4819-86-6-708. [DOI] [PubMed] [Google Scholar]
  6. Gerding D. N., Peterson L. R., Legler D. C., Hall W. H., Schierl E. A. Ascitic fluid cephalosporin concentrations: influence of protein binding and serum pharmacokinetics. Antimicrob Agents Chemother. 1978 Aug;14(2):234–239. doi: 10.1128/aac.14.2.234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kozak A. J., Gerding D. N., Peterson L. R., Hall W. H. Gentamicin intravenous infusion rate: effect on interstitial fluid concentration. Antimicrob Agents Chemother. 1977 Nov;12(5):606–608. doi: 10.1128/aac.12.5.606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kunin C. M. Dosage schedules of antimicrobial agents: a historical review. Rev Infect Dis. 1981 Jan-Feb;3(1):4–11. doi: 10.1093/clinids/3.1.4. [DOI] [PubMed] [Google Scholar]
  9. PLORDE J. J., GARCIA M., PETERSDORF R. G. STUDIES ON THE PATHOGENESIS OF MENINGITIS. IV. PENICILLIN LEVELS IN THE CEREBROSPINAL FLUID IN EXPERIMENTAL MENINGITIS. J Lab Clin Med. 1964 Dec;64:960–969. [PubMed] [Google Scholar]
  10. Peterson L. R., Gerding D. N., Fasching C. E. Effects of method of antibiotic administration on extravascular penetration: cross-over study of cefazolin given by intermittent injection or constant infusion. J Antimicrob Chemother. 1981 Jan;7(1):71–79. doi: 10.1093/jac/7.1.71. [DOI] [PubMed] [Google Scholar]
  11. Peterson L. R., Gerding D. N. Prediction of cefazolin penetration in high- and low-protein-containing extravascular fluid: new method for performing simultaneous studies. Antimicrob Agents Chemother. 1978 Oct;14(4):533–538. doi: 10.1128/aac.14.4.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Sabath L. D. The assay of antimicrobial compounds. Hum Pathol. 1976 May;7(3):287–295. doi: 10.1016/s0046-8177(76)80039-1. [DOI] [PubMed] [Google Scholar]
  14. Thys J. P., Vanderkelen B., Klastersky J. Pharmacological study of cefazolin during intermittent and continuous infusion: a crossover investigation in humans. Antimicrob Agents Chemother. 1976 Sep;10(3):395–398. doi: 10.1128/aac.10.3.395. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES