Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1992 Jan;36(1):126–131. doi: 10.1128/aac.36.1.126

Disposition of cefpodoxime proxetil in healthy volunteers and patients with impaired renal function.

J V St Peter 1, M T Borin 1, G S Hughes 1, J S Kelloway 1, B E Shapiro 1, C E Halstenson 1
PMCID: PMC189239  PMID: 1590677

Abstract

The disposition of cefpodoxime in 24 subjects with various degrees of renal function after administration of a single oral dose of 200 mg of cefpodoxime proxetil (equivalent to 200 mg of cefpodoxime activity) was studied. Subjects were assigned to one of four groups (six per group): group I, normal renal function (creatinine clearance [CLCR], greater than ml/min); group II, mild renal impairment (CLCR, 50 to 80 ml/min); group III, moderate renal impairment (CLCR, 30 to 49 ml/min); or group IV, severe renal impairment (CLCR, 5 to 29 ml/min). Although cefpodoxime terminal elimination half-life in group I (2.55 +/- 0.25 h [mean +/- standard deviation]) was not significantly different from that in group II (3.53 +/- 0.74 h), the half-life values for group III (5.90 +/- 1.67 h) and group IV (9.80 +/- 1.21 h) were significantly prolonged compared with those of group I. The mean absorption rate constant was similar among groups and ranged from 0.68 to 0.85 h-1. All groups exhibited absorption lag-times which were comparable (0.30 to 0.41 h), and the apparent volume of distribution was similar among groups. Cefpodoxime apparent total body clearance (CLP/F) values in groups II, III, and IV (132 +/- 29, 112 +/- 41, and 55.7 +/- 9.9 ml/min, respectively) were significantly lower than that in group I (238 +/- 44 ml/min). Cefpodoxime CLP/F was positively correlated with CLCR (r2 = 0.79; P less than 0.05): CLP/F = (1.9 CLCR) + 18.4. Renal clearance also declined with decreasing renal function. Adjustments in cefpodoxime organism and on the site and severity of infection. Simulated plasma concentration-time data from this study suggest that 200 mg of cefpodoxime proxetil administered every 12 to 24 h to subjects with CLcr between 30 and 49 ml/min and 200-mg dose taken every 24 h by subjects with CLcr between 5 and 29 ml/min will maintain cefpodoxime concentration in plasma similar to those in subjects with normal renal function who receive a standard dosage mg every 12 h.

Full text

PDF
126

Selected References

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

  1. Backhouse C., Wade A., Williamson P., Tremblay D., Lenfant B. Multiple dose pharmacokinetics of cefpodoxime in young adult and elderly patients. J Antimicrob Chemother. 1990 Dec;26 (Suppl E):29–34. doi: 10.1093/jac/26.suppl_e.29. [DOI] [PubMed] [Google Scholar]
  2. Fass R. J., Helsel V. L. In vitro activity of U-76,252 (CS-807), a new oral cephalosporin. Antimicrob Agents Chemother. 1988 Jul;32(7):1082–1085. doi: 10.1128/aac.32.7.1082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Guay D. R., Meatherall R. C., Harding G. K., Brown G. R. Pharmacokinetics of cefixime (CL 284,635; FK 027) in healthy subjects and patients with renal insufficiency. Antimicrob Agents Chemother. 1986 Sep;30(3):485–490. doi: 10.1128/aac.30.3.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hughes G. S., Heald D. L., Barker K. B., Patel R. K., Spillers C. R., Watts K. C., Batts D. H., Euler A. R. The effects of gastric pH and food on the pharmacokinetics of a new oral cephalosporin, cefpodoxime proxetil. Clin Pharmacol Ther. 1989 Dec;46(6):674–685. doi: 10.1038/clpt.1989.204. [DOI] [PubMed] [Google Scholar]
  5. Jones R. N., Barry A. L. Antimicrobial activity and disk diffusion susceptibility testing of U-76,253A (R-3746), the active metabolite of the new cephalosporin ester, U-76,252 (CS-807). Antimicrob Agents Chemother. 1988 Apr;32(4):443–449. doi: 10.1128/aac.32.4.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Jones R. N., Barry A. L., Pfaller M., Allen S. D., Ayers L. W., Fuchs P. C. Antimicrobial activity of U-76,252 (CS-807), a new orally administered cephalosporin ester, including recommendations for MIC quality control. Diagn Microbiol Infect Dis. 1988 Jan;9(1):59–63. doi: 10.1016/0732-8893(88)90063-6. [DOI] [PubMed] [Google Scholar]
  7. Kneer J., Tam Y. K., Blouin R. A., Frey F. J., Keller E., Stathakis C., Luginbuehl B., Stoeckel K. Pharmacokinetics of intravenous cefetamet and oral cefetamet pivoxil in patients with renal insufficiency. Antimicrob Agents Chemother. 1989 Nov;33(11):1952–1957. doi: 10.1128/aac.33.11.1952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. O'Neill P., Nye K., Douce G., Andrews J., Wise R. Pharmacokinetics and inflammatory fluid penetration of cefpodoxime proxetil in volunteers. Antimicrob Agents Chemother. 1990 Feb;34(2):232–234. doi: 10.1128/aac.34.2.232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Tremblay D., Dupront A., Ho C., Coussediere D., Lenfant B. Pharmacokinetics of cefpodoxime in young and elderly volunteers after single doses. J Antimicrob Chemother. 1990 Dec;26 (Suppl E):21–28. doi: 10.1093/jac/26.suppl_e.21. [DOI] [PubMed] [Google Scholar]
  10. Utsui Y., Inoue M., Mitsuhashi S. In vitro and in vivo antibacterial activities of CS-807, a new oral cephalosporin. Antimicrob Agents Chemother. 1987 Jul;31(7):1085–1092. doi: 10.1128/aac.31.7.1085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Wiedemann B., Jansen A. Antibacterial activity of cefpodoxime proxetil in a pharmacokinetic in-vitro model. J Antimicrob Chemother. 1990 Jul;26(1):71–79. doi: 10.1093/jac/26.1.71. [DOI] [PubMed] [Google Scholar]
  12. Yokota T., Suzuki E., Arai K. Cefpodoxime proxetil, its in vitro antibacterial activity, affinity to bacterial penicillin-binding proteins, and synergy of bactericidal activity with serum complement and mouse-cultured macrophages. Drugs Exp Clin Res. 1988;14(8):495–500. [PubMed] [Google Scholar]

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

RESOURCES