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. 1992 Mar;36(3):521–526. doi: 10.1128/aac.36.3.521

Bactericidal titers of loracarbef (LY 163892) in serum and killing rates in volunteers receiving 400 versus 200 milligrams.

P Van der Auwera 1
PMCID: PMC190550  PMID: 1622160

Abstract

In a randomized crossover trial, six volunteers received 200- and 400-mg doses of loracarbef (LY 163892), a new oral cephalosporin. Mean +/- standard error of the mean concentrations in serum obtained after 1.5 and 3 h were 13.2 +/- 2.8 and 4.3 +/- 0.7 mg/liter, respectively, after the 400-mg dose and 6.9 +/- 1.0 and 1.7 +/- 0.2 mg/liter, respectively, after the 200-mg dose. Bactericidal reciprocal titers measured against respiratory pathogens in serum suggested that loracarbef would be highly effective against Streptococcus pneumoniae and Streptococcus pyogenes (median titers, 8 to 128 at 1.5 h and less than 2 to 32 at 3 h) and beta-lactamase-negative Haemophilus influenzae (median titers, 4 at 1.5 h and 2 to 4 at 3 h). Other species (Branhamella catarrhalis, Streptococcus anginosus, Staphylococcus aureus) were associated with lower bactericidal titers. Killing curves performed against 12 strains demonstrated that the bioactivity of loracarbef (measured by the reduction in the area under the control growth curve) was significantly correlated with the concentration/MIC ratio, whereas the initial rate of killing was not, once the concentration was greater than the MIC. Our results suggest that administration of 400 mg of loracarbef every 8 h might be associated with more favorable pharmacodynamic parameters against target bacteria.

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Selected References

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  1. Barbhaiya R. H., Shukla U. A., Gleason C. R., Shyu W. C., Pittman K. A. Comparison of the effects of food on the pharmacokinetics of cefprozil and cefaclor. Antimicrob Agents Chemother. 1990 Jun;34(6):1210–1213. doi: 10.1128/aac.34.6.1210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barbhaiya R. H., Shukla U. A., Gleason C. R., Shyu W. C., Wilber R. B., Martin R. R., Pittman K. A. Phase I study of multiple-dose cefprozil and comparison with cefaclor. Antimicrob Agents Chemother. 1990 Jun;34(6):1198–1203. doi: 10.1128/aac.34.6.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bérubé D., Kirouac D., Croteau D., Bergeron M. G., Lebel M. Plasma bactericidal activity after administration of erythromycin estolate and erythromycin ethylsuccinate to healthy volunteers. Antimicrob Agents Chemother. 1988 Aug;32(8):1227–1230. doi: 10.1128/aac.32.8.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Drake T. A., Hackbarth C. J., Sande M. A. Value of serum tests in combined drug therapy of endocarditis. Antimicrob Agents Chemother. 1983 Nov;24(5):653–657. doi: 10.1128/aac.24.5.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Drusano G. L. Role of pharmacokinetics in the outcome of infections. Antimicrob Agents Chemother. 1988 Mar;32(3):289–297. doi: 10.1128/aac.32.3.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Jorgensen J. H., Redding J. S., Maher L. A., Howell A. W. Improved medium for antimicrobial susceptibility testing of Haemophilus influenzae. J Clin Microbiol. 1987 Nov;25(11):2105–2113. doi: 10.1128/jcm.25.11.2105-2113.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Knapp C. C., Washington J. A., 2nd In vitro activities of LY163892, cefaclor, and cefuroxime. Antimicrob Agents Chemother. 1988 Jan;32(1):131–133. doi: 10.1128/aac.32.1.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kusmiesz H., Shelton S., Brown O., Manning S., Nelson J. D. Loracarbef concentrations in middle ear fluid. Antimicrob Agents Chemother. 1990 Oct;34(10):2030–2031. doi: 10.1128/aac.34.10.2030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Nelson J. D., Shelton S., Kusmiesz H. Pharmacokinetics of LY163892 in infants and children. Antimicrob Agents Chemother. 1988 Nov;32(11):1738–1739. doi: 10.1128/aac.32.11.1738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Pearson R. D., Steigbigel R. T., Davis H. T., Chapman S. W. Method of reliable determination of minimal lethal antibiotic concentrations. Antimicrob Agents Chemother. 1980 Nov;18(5):699–708. doi: 10.1128/aac.18.5.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Reller L. B., Stratton C. W. Serum dilution test for bactericidal activity. II. Standardization and correlation with antimicrobial assays and susceptibility tests. J Infect Dis. 1977 Aug;136(2):196–204. doi: 10.1093/infdis/136.2.196. [DOI] [PubMed] [Google Scholar]
  12. Sculier J. P., Klastersky J. Significance of serum bactericidal activity in gram-negative bacillary bacteremia in patients with and without granulocytopenia. Am J Med. 1984 Mar;76(3):429–435. doi: 10.1016/0002-9343(84)90662-4. [DOI] [PubMed] [Google Scholar]
  13. Van der Auwera P., Klastersky J., Lagast H., Husson M. Serum bactericidal activity and killing rate for volunteers receiving imipenem, imipenem plus amikacin, and ceftazidime plus amikacin against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1986 Jul;30(1):122–126. doi: 10.1128/aac.30.1.122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Van der Auwera P., Klastersky J. Serum bactericidal activity and postantibiotic effect in serum of patients with urinary tract infection receiving high-dose amikacin. Antimicrob Agents Chemother. 1987 Jul;31(7):1061–1068. doi: 10.1128/aac.31.7.1061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Van der Auwera P., Van Laethem Y., Defresne N., Husson M., Klastersky J. Comparative serum bactericidal activity against test anaerobes in volunteers receiving imipenem, clindamycin, latamoxef and metronidazole. J Antimicrob Chemother. 1987 Feb;19(2):205–210. doi: 10.1093/jac/19.2.205. [DOI] [PubMed] [Google Scholar]
  16. Wise R. The pharmacokinetics of the oral cephalosporins--a review. J Antimicrob Chemother. 1990 Dec;26 (Suppl E):13–20. doi: 10.1093/jac/26.suppl_e.13. [DOI] [PubMed] [Google Scholar]
  17. Wolfson J. S., Swartz M. N. Drug therapy. Serum bactericidal activity as a monitor of antibiotic therapy. N Engl J Med. 1985 Apr 11;312(15):968–975. doi: 10.1056/NEJM198504113121507. [DOI] [PubMed] [Google Scholar]

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