Abstract
The effect of extravascular fluid protein concentration and drug-protein binding was studied in rabbits with subcutaneously implanted Visking chambers. Chambers containing serum or saline were simultaneously studied in three animals by injecting cefazolin (30 mg/kg) intramuscularly every 4 h for four doses. Five additional animals were then studied for an 8-h period while receiving two doses of cefazolin. Peak and trough serum and chamber fluid were assayed for cefazolin concentration. The three-animal experiment demonstrated that equilibrium in the subcutaneous chambers was reached after two intramuscular injections and that the extravascular fluid levels were stable in comparison to the wide fluctuation of the serum levels. The five-animal experiment demonstrated that after two doses the serum-filled chambers contained 12.9 μg of cefazolin per ml, whereas saline-filled chambers contained 1.8 μg of cefazolin per ml. Ratios of chamber to peak serum for the second study were 12.4% for serum chambers and 1.7% for saline chambers. The cefazolin concentration in high-and low-protein extravascular fluid in both studies could be predicted from the logarithmic mean of the peak and trough serum cefazolin concentration and the antibiotic binding to rabbit serum and extravascular fluid proteins. These observations explain the previously published apparent discrepancies seen in studies of extravascular penetration of highly protein-bound antibiotics such as cefazolin.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Carbon C., Contrepois A., Brion N., Lamotte-Barrillon S. Penetration of cefazolin, cephaloridine, and cefamandole into interstitial fluid in rabbits. Antimicrob Agents Chemother. 1977 Apr;11(4):594–598. doi: 10.1128/aac.11.4.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cole D. R., Pung J. Penetration of cefazolin into pleural fluid. Antimicrob Agents Chemother. 1977 Jun;11(6):1033–1035. doi: 10.1128/aac.11.6.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GLADSTONE G. P., GLENCROSS E. J. Growth and toxin production of staphylococci in cellophane sacs in vivo. Br J Exp Pathol. 1960 Jun;41:313–333. [PMC free article] [PubMed] [Google Scholar]
- Gerding D. N., Hall W. H., Schierl E. A., Manion R. E. Cephalosporin and aminoglycoside concentrations in peritoneal capsular fluid in rabbits. Antimicrob Agents Chemother. 1976 Dec;10(6):902–911. doi: 10.1128/aac.10.6.902. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerding D. N., Hall W. H. The penetration of antibiotics into peritoneal fluid. Bull N Y Acad Med. 1975 Oct;51(9):1016–1019. [PMC free article] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Nishida M., Murakawa T. Exudate levels and bactericidal activity of cefazolin in a new local infection system using rat granuloma pouches. Antimicrob Agents Chemother. 1977 Jun;11(6):1042–1048. doi: 10.1128/aac.11.6.1042. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Tan J. S., Salstrom S. J. Levels of carbenicillin, ticarcillin, cephalothin, cefazolin, cefamandole, gentamicin, tobramycin, and amikacin in human serum and interstitial fluid. Antimicrob Agents Chemother. 1977 Apr;11(4):698–700. doi: 10.1128/aac.11.4.698. [DOI] [PMC free article] [PubMed] [Google Scholar]