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. 1992 Jul;36(7):1387–1391. doi: 10.1128/aac.36.7.1387

Pharmacokinetics of cefepime in patients undergoing continuous ambulatory peritoneal dialysis.

R H Barbhaiya 1, C A Knupp 1, M Pfeffer 1, D Zaccardelli 1, G M Dukes 1, W Mattern 1, K A Pittman 1, L J Hak 1
PMCID: PMC191591  PMID: 1510432

Abstract

The pharmacokinetics of cefepime were studied in 10 male patients receiving continuous ambulatory peritoneal dialysis therapy. Five patients received a single 1,000-mg dose and the other five received a single 2,000-mg dose; all doses were given as 30-min intravenous infusions. Serial plasma, urine, and peritoneal dialysate samples were collected; and the concentrations of cefepime in these fluids were measured over 72 h by using a high-performance liquid chromatographic assay with UV detection. Pharmacokinetic parameters were calculated by noncompartmental methods. The peak concentrations in plasma and the areas under the plasma concentration-versus-time curve for the 2,000-mg dose group were twice as high as those observed for the 1,000-mg dose group. The elimination half-life of cefepime was about 18 h and was independent of the dose. The steady-state volume of distribution was about 22 liters, and values for the 1,000- and 2,000-mg doses were not significantly different. The values for total body clearance and peritoneal dialysis clearance were about 15 and 4 ml/min, respectively. No dose dependency was observed for the clearance estimates. Over the 72-h sampling period, about 26% of the dose was excreted intact into the peritoneal dialysis fluid. For 48 h postdose, mean concentrations of cefepime in dialysate at the end of each dialysis interval exceeded the reported MICs for 90% of the isolates (MIC90s) for bacteria which commonly cause peritonitis resulting from continuous peritoneal dialysis. A parenteral dose of 1,000 or 2,000 mg of cefepime every 48 h would maintain the antibiotic levels in plasma and peritoneal fluid above the MIC90s for the most susceptible bacteria for the treatment of systemic and intraperitoneal infections [corrected].

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Selected References

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  1. Barbhaiya R. H., Forgue S. T., Gleason C. R., Knupp C. A., Pittman K. A., Weidler D. J., Martin R. R. Safety, tolerance, and pharmacokinetic evaluation of cefepime after administration of single intravenous doses. Antimicrob Agents Chemother. 1990 Jun;34(6):1118–1122. doi: 10.1128/aac.34.6.1118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barbhaiya R. H., Forgue S. T., Gleason C. R., Knupp C. A., Pittman K. A., Weidler D. J., Movahhed H., Tenney J., Martin R. R. Pharmacokinetics of cefepime after single and multiple intravenous administrations in healthy subjects. Antimicrob Agents Chemother. 1992 Mar;36(3):552–557. doi: 10.1128/aac.36.3.552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barbhaiya R. H., Forgue S. T., Shyu W. C., Papp E. A., Pittman K. A. High-pressure liquid chromatographic analysis of BMY-28142 in plasma and urine. Antimicrob Agents Chemother. 1987 Jan;31(1):55–59. doi: 10.1128/aac.31.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barbhaiya R. H., Knupp C. A., Forgue S. T., Matzke G. R., Guay D. R., Pittman K. A. Pharmacokinetics of cefepime in subjects with renal insufficiency. Clin Pharmacol Ther. 1990 Sep;48(3):268–276. doi: 10.1038/clpt.1990.149. [DOI] [PubMed] [Google Scholar]
  5. Barbhaiya R. H., Knupp C. A., Forgue S. T., Matzke G. R., Halstenson C. E., Opsahl J. A., Pittman K. A. Disposition of the cephalosporin cefepime in normal and renally impaired subjects. Drug Metab Dispos. 1991 Jan-Feb;19(1):68–73. [PubMed] [Google Scholar]
  6. Barbhaiya R. H., Knupp C. A., Tenney J., Martin R. R., Weidler D. J., Pittman K. A. Safety, tolerance, and pharmacokinetics of cefepime administered intramuscularly to healthy subjects. J Clin Pharmacol. 1990 Oct;30(10):900–910. doi: 10.1002/j.1552-4604.1990.tb03569.x. [DOI] [PubMed] [Google Scholar]
  7. Fuchs P. C., Jones R. N., Barry A. L., Thornsberry C. Evaluation of the in vitro activity of BMY-28142, a new broad-spectrum cephalosporin. Antimicrob Agents Chemother. 1985 May;27(5):679–682. doi: 10.1128/aac.27.5.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gross M. L., Somani P., Ribner B. S., Raeader R., Freimer E. H., Higgins J. T., Jr Ceftizoxime elimination kinetics in continuous ambulatory peritoneal dialysis. Clin Pharmacol Ther. 1983 Nov;34(5):673–680. doi: 10.1038/clpt.1983.231. [DOI] [PubMed] [Google Scholar]
  9. Johnson C. A., Zimmerman S. W., Reitberg D. P., Whall T. J., Leggett J. E., Craig W. A. Pharmacokinetics and pharmacodynamics of cefoperazone-sulbactam in patients on continuous ambulatory peritoneal dialysis. Antimicrob Agents Chemother. 1988 Jan;32(1):51–56. doi: 10.1128/aac.32.1.51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Johnson C. A., Zimmerman S. W., Rogge M. The pharmacokinetics of antibiotics used to treat peritoneal dialysis-associated peritonitis. Am J Kidney Dis. 1984 Jul;4(1):3–17. doi: 10.1016/s0272-6386(84)80020-7. [DOI] [PubMed] [Google Scholar]
  11. Kessler R. E., Bies M., Buck R. E., Chisholm D. R., Pursiano T. A., Tsai Y. H., Misiek M., Price K. E., Leitner F. Comparison of a new cephalosporin, BMY 28142, with other broad-spectrum beta-lactam antibiotics. Antimicrob Agents Chemother. 1985 Feb;27(2):207–216. doi: 10.1128/aac.27.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Koup J. R., Keller E., Neumann H., Stoeckel K. Ceftriaxone pharmacokinetics during peritoneal dialysis. Eur J Clin Pharmacol. 1986;30(3):303–307. doi: 10.1007/BF00541533. [DOI] [PubMed] [Google Scholar]
  13. Oreopoulos D. G., Robson M., Faller B., Ogilvie R., Rapoport A., deVeber G. A. Continuous ambulatory peritoneal dialysis: a new era in the treatment of chronic renal failure. Clin Nephrol. 1979 Mar;11(3):125–128. [PubMed] [Google Scholar]
  14. Peterson P. K., Matzke G., Keane W. F. Current concepts in the management of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. Rev Infect Dis. 1987 May-Jun;9(3):604–612. doi: 10.1093/clinids/9.3.604. [DOI] [PubMed] [Google Scholar]
  15. Phelps D. J., Carlton D. D., Farrell C. A., Kessler R. E. Affinity of cephalosporins for beta-lactamases as a factor in antibacterial efficacy. Antimicrob Agents Chemother. 1986 May;29(5):845–848. doi: 10.1128/aac.29.5.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Popovich R. P., Moncrief J. W., Nolph K. D., Ghods A. J., Twardowski Z. J., Pyle W. K. Continuous ambulatory peritoneal dialysis. Ann Intern Med. 1978 Apr;88(4):449–456. doi: 10.7326/0003-4819-88-4-449. [DOI] [PubMed] [Google Scholar]
  17. Riegelman S., Collier P. The application of statistical moment theory to the evaluation of in vivo dissolution time and absorption time. J Pharmacokinet Biopharm. 1980 Oct;8(5):509–534. doi: 10.1007/BF01059549. [DOI] [PubMed] [Google Scholar]
  18. Rubin J., Ray R., Barnes T., Bower J. Peritoneal abnormalities during infectious episodes of continuous ambulatory peritoneal dialysis. Nephron. 1981;29(3-4):124–127. doi: 10.1159/000182328. [DOI] [PubMed] [Google Scholar]
  19. Rubin J., Rogers W. A., Taylor H. M., Everett E. D., Prowant B. F., Fruto L. V., Nolph K. D. Peritonitis during continuous ambulatory peritoneal dialysis. Ann Intern Med. 1980 Jan;92(1):7–13. doi: 10.7326/0003-4819-92-1-7. [DOI] [PubMed] [Google Scholar]
  20. Tourkantonis A., Nicolaidis P. Pharmacokinetics of ceftazidime in patients undergoing peritoneal dialysis. J Antimicrob Chemother. 1983 Jul;12 (Suppl A):263–267. doi: 10.1093/jac/12.suppl_a.263. [DOI] [PubMed] [Google Scholar]
  21. Tsuji A., Maniatis A., Bertram M. A., Young L. S. In vitro activity of BMY-28142 in comparison with those of other beta-lactam antimicrobial agents. Antimicrob Agents Chemother. 1985 Apr;27(4):515–519. doi: 10.1128/aac.27.4.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Washington T. G., Eggleston M. The use of intraperitoneal antibiotics to treat dialysis-associated peritonitis. Infect Control. 1988 Jan;9(1):37–39. [PubMed] [Google Scholar]

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