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. 1997 Aug;41(8):1783–1787. doi: 10.1128/aac.41.8.1783

Pharmacokinetics of intravenously and intramuscularly administered cefepime in infants and children.

M D Reed 1, T S Yamashita 1, C K Knupp 1, J M Veazey Jr 1, J L Blumer 1
PMCID: PMC164005  PMID: 9257761

Abstract

The pharmacokinetic characteristics of cefepime were determined after first dose (n = 35) and again under steady-state conditions (n = 31) with a group of 37 infants and children. In eight subjects, a cefepime dose given by intramuscular injection was substituted for an intravenous dose, and disposition characteristics were studied again. Study subjects ranged in age from 2.1 months to 16.4 years, and all had normal renal function. Each patient received 50 mg of cefepime/kg of body weight intravenously every 8 h, up to a total maximum individual dose of 2 g. With the exception of one study patient who received a single cefepime dose for surgical prophylaxis, the patients received cefepime for 2 to 13 days. Elimination half-life (t1/2), steady-state volume of distribution, total body clearance, and renal clearance after first dose administration averaged 1.7 h, 0.35 liter/kg, and 3.1 and 1.9 ml/min/kg, respectively. Although cefepime t1/2 and mean residence time (MRT) were slightly longer for subjects <6 months of age than for older subjects, no differences in cefepime disposition characteristics between first dose and steady-state evaluations were observed. t1/2 (1.8 versus 1.9 h) and MRT (2.3 versus 3.2 h) were slightly prolonged after intramuscular administration, reflecting the influence of absorption from the intramuscular injection site on cefepime elimination. Bioavailability after intramuscular administration averaged 82% (range, 61 to 124%). Fifty-seven percent of the first dose and 88.9% of the last dose were recovered as unchanged drug in urine over the 8- and 24-h sampling periods, respectively. These pharmacokinetic data support a single cefepime dosing strategy for patients > or =2 months of age. The integration of the cefepime pharmacokinetic data generated in our study with the MICs for important pathogens responsible for infections in infants and children supports the administration of a dose of 50 mg of cefepime/kg every 12 h for patients > or =2 months of age to treat infections caused by pathogens for which cefepime MICs are < or =8 mg/liter.

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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., 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. Barradell L. B., Bryson H. M. Cefepime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1994 Mar;47(3):471–505. doi: 10.2165/00003495-199447030-00007. [DOI] [PubMed] [Google Scholar]
  7. Blumer J. L., Aronoff S. C., Myers C. M., O'Brien C. A., Klinger J. D., Reed M. D. Pharmacokinetics and cerebrospinal fluid penetration of ceftazidime in children with meningitis. Dev Pharmacol Ther. 1985;8(4):219–231. doi: 10.1159/000457041. [DOI] [PubMed] [Google Scholar]
  8. Byron P. R., Notari R. E. Critical analysis of "flip-flop" phenomenon in two-compartment pharmacokinetic model. J Pharm Sci. 1976 Aug;65(8):1140–1144. doi: 10.1002/jps.2600650804. [DOI] [PubMed] [Google Scholar]
  9. Craig W. A. Interrelationship between pharmacokinetics and pharmacodynamics in determining dosage regimens for broad-spectrum cephalosporins. Diagn Microbiol Infect Dis. 1995 May-Jun;22(1-2):89–96. doi: 10.1016/0732-8893(95)00053-d. [DOI] [PubMed] [Google Scholar]
  10. Cunha B. A., Gill M. V. Cefepime. Med Clin North Am. 1995 Jul;79(4):721–732. doi: 10.1016/s0025-7125(16)30035-9. [DOI] [PubMed] [Google Scholar]
  11. Drusano G. L. Human pharmacodynamics of beta-lactams, aminoglycosides and their combination. Scand J Infect Dis Suppl. 1990;74:235–248. [PubMed] [Google Scholar]
  12. Kalman D., Barriere S. L., Johnson B. L., Jr Pharmacokinetic disposition and bactericidal activities of cefepime, ceftazidime, and cefoperazone in serum and blister fluid. Antimicrob Agents Chemother. 1992 Feb;36(2):453–457. doi: 10.1128/aac.36.2.453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kearns G. L., Reed M. D. Clinical pharmacokinetics in infants and children. A reappraisal. Clin Pharmacokinet. 1989;17 (Suppl 1):29–67. doi: 10.2165/00003088-198900171-00005. [DOI] [PubMed] [Google Scholar]
  14. Kearns G. L., Young R. A., Jacobs R. F. Cefotaxime dosage in infants and children. Pharmacokinetic and clinical rationale for an extended dosage interval. Clin Pharmacokinet. 1992 Apr;22(4):284–297. doi: 10.2165/00003088-199222040-00004. [DOI] [PubMed] [Google Scholar]
  15. Klein N. C., Cunha B. A. Third-generation cephalosporins. Med Clin North Am. 1995 Jul;79(4):705–719. doi: 10.1016/s0025-7125(16)30034-7. [DOI] [PubMed] [Google Scholar]
  16. Neu H. C. Pathophysiologic basis for the use of third-generation cephalosporins. Am J Med. 1990 Apr 9;88(4A):3S–11S. doi: 10.1016/0002-9343(90)90321-4. [DOI] [PubMed] [Google Scholar]
  17. Neu H. C. The crisis in antibiotic resistance. Science. 1992 Aug 21;257(5073):1064–1073. doi: 10.1126/science.257.5073.1064. [DOI] [PubMed] [Google Scholar]
  18. Pechère J. C., Wilson W., Neu H. Laboratory assessment of antibacterial activity of zwitterionic 7-methoxyimino cephalosporins. J Antimicrob Chemother. 1995 Nov;36(5):757–771. doi: 10.1093/jac/36.5.757. [DOI] [PubMed] [Google Scholar]
  19. Reed M. D., Aronoff S. C., Myers C. M., Husak M. P., Bertino J. S., Jr, Blumer J. L. Developmental pharmacokinetics of moxalactam. Antimicrob Agents Chemother. 1983 Sep;24(3):383–387. doi: 10.1128/aac.24.3.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reed M. D., Besunder J. B. Developmental pharmacology: ontogenic basis of drug disposition. Pediatr Clin North Am. 1989 Oct;36(5):1053–1074. doi: 10.1016/s0031-3955(16)36757-8. [DOI] [PubMed] [Google Scholar]
  21. Sanders C. C. Cefepime: the next generation? Clin Infect Dis. 1993 Sep;17(3):369–379. [PubMed] [Google Scholar]
  22. Sanders C. C., Sanders W. E., Jr beta-Lactam resistance in gram-negative bacteria: global trends and clinical impact. Clin Infect Dis. 1992 Nov;15(5):824–839. doi: 10.1093/clind/15.5.824. [DOI] [PubMed] [Google Scholar]
  23. Sáez-Llorens X., Castaño E., García R., Báez C., Pérez M., Tejeira F., McCracken G. H., Jr Prospective randomized comparison of cefepime and cefotaxime for treatment of bacterial meningitis in infants and children. Antimicrob Agents Chemother. 1995 Apr;39(4):937–940. doi: 10.1128/aac.39.4.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Thornsberry C. Trends in antimicrobial resistance among today's bacterial pathogens. Pharmacotherapy. 1995 Jan-Feb;15(1 Pt 2):3S–8S. [PubMed] [Google Scholar]
  25. Williams J. D. Classification of cephalosporins. Drugs. 1987;34 (Suppl 2):15–22. doi: 10.2165/00003495-198700342-00004. [DOI] [PubMed] [Google Scholar]
  26. Yamashita T. S., Lee H. L., Reed M. D. A versatile computational method for the determination of areas under the curve and moment curve following multidose drug administration. Int J Biomed Comput. 1988 Dec;23(3-4):239–249. doi: 10.1016/0020-7101(88)90017-7. [DOI] [PubMed] [Google Scholar]

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