Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1994 Jun;38(6):1219–1224. doi: 10.1128/aac.38.6.1219

Single-dose pharmacokinetics of oral fleroxacin in bacteremic patients.

J Schrenzel 1, F Cerruti 1, M Herrmann 1, T Leemann 1, E Weidekamm 1, R Portmann 1, B Hirschel 1, D P Lew 1
PMCID: PMC188189  PMID: 8092817

Abstract

Fleroxacin is a new broad-spectrum quinolone which can be given by the oral route. The present study was designed to assess the influence of bacteremia on the pharmacokinetics of a single oral dose of fleroxacin. Thirteen patients with proven bacteremia (one or more pairs of positive blood cultures, no hypotension) were given a single 400-mg fleroxacin dose orally on two occasions while also receiving standard antibiotic therapy. The first dose was administered 12 to 36 h after the last positive blood culture was drawn (day 1), and a second dose was administered 7 days later (day 7 +/- 2) to compare the pharmacokinetics between the acute and the convalescent phases of the disease. Following each administration of fleroxacin, serial plasma samples were collected for up to 72 h and were analyzed for unchanged drug by a reversed phase high-pressure liquid chromatography technique. There were no significant changes in the following pharmacokinetic parameters (mean standard deviation) the maximum concentration of drug in serum (6.4 +/- 1.5 versus 6.7 +/- 1.9 mg/liter), the minimum concentration of drug in serum, defined as the concentration of drug in serum at 24 h postdose (3.0 +/- 1.7 versus 2.5 +/- 1.2 mg/liter), the time to the maximum concentration of drug in serum (2.3 +/- 1.4 versus 2.0 +/- 1.2 h), and the elimination half-life (19.7 +/- 8.0 versus 17.9 +/- 6.9 h). Fleroxacin clearances were compared for each individual patient. A positive correlation (R2 = 0.787) was found between the values measured on day 1 and day 7. Oral clearance of fleroxacin (CL = CL/F, where F is bioavailability was slightly, but not significantly, reduced during the bacteremic phase (oral clearance, 43.8+/- 23.5 versus 48.5 +/- 17.5 ml/min.). When compared with previous results obtained in healthy young subjects, longer times to the maximum concentration of drug in serum and elimination half-lives and higher areas under the curve were observed. This could be due to the bacteremic state, the old age of the patients (mean, 66 years), and the low renal clearance (mean calculated creatinine clearance, 71.1 ml/min). A single oral dose of 400 mg of fleroxacin provides sufficient levels in serum to cover susceptible microorganisms for at least 24 h in bacteremic patients. Renal function appeared to be the key element that had to be taken into consideration to adapt fleroxacin dosage profiles in our patient population. Bacteremia itself appeared to amplify that phenomenon, but to a much lesser extent than renal function did.

Full text

PDF
1219

Selected References

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

  1. Aarbakke J., Gadeholt G., Olsen H. Lack of effect of fever on antipyrine oxidation in the rat. Eur J Pharmacol. 1978 May 1;49(1):31–37. doi: 10.1016/0014-2999(78)90219-4. [DOI] [PubMed] [Google Scholar]
  2. Abdullah A. S., Baggot J. D. Influence of Escherichia coli endotoxin-induced fever on pharmacokinetics of imidocarb in dogs and goats. Am J Vet Res. 1984 Dec;45(12):2645–2648. [PubMed] [Google Scholar]
  3. BLICKENSTAFF D., GROSSMAN M. I. A quantitative study of the reduction of gastric acid secretion associated with pyrexia. Am J Physiol. 1950 Mar;160(3):567–571. doi: 10.1152/ajplegacy.1950.160.3.567. [DOI] [PubMed] [Google Scholar]
  4. Ballard B. E. Pharmacokinetics and temperature. J Pharm Sci. 1974 Sep;63(9):1345–1358. doi: 10.1002/jps.2600630903. [DOI] [PubMed] [Google Scholar]
  5. Barry A. L., Fuchs P. C. In vitro activities of sparfloxacin, tosufloxacin, ciprofloxacin, and fleroxacin. Antimicrob Agents Chemother. 1991 May;35(5):955–960. doi: 10.1128/aac.35.5.955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Beresford C. H., Neale R. J., Brooks O. G. Iron absorption and pyrexia. Lancet. 1971 Mar 20;1(7699):568–572. doi: 10.1016/s0140-6736(71)91165-2. [DOI] [PubMed] [Google Scholar]
  7. Beskid G., Prosser B. L. A multicenter study on the comparative in vitro activity of fleroxacin and three other quinolones: an interim report from 27 centers. Am J Med. 1993 Mar 22;94(3A):2S–8S. [PubMed] [Google Scholar]
  8. Blouin R. A., Hamelin B. A., Smith D. A., Foster T. S., John W. J., Welker H. A. Fleroxacin pharmacokinetics in patients with liver cirrhosis. Antimicrob Agents Chemother. 1992 Mar;36(3):632–638. doi: 10.1128/aac.36.3.632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Blum R. A. Influence of renal function on the pharmacokinetics of lomefloxacin compared with other fluoroquinolones. Am J Med. 1992 Apr 6;92(4A):18S–21S. doi: 10.1016/0002-9343(92)90302-r. [DOI] [PubMed] [Google Scholar]
  10. Cakmakci M., Gossweiler L., Schilling J., Schlumpf R., Geroulanos S. Penetration of fleroxacin into human lung, muscle, and fat tissue. Drugs Exp Clin Res. 1992;18(7):299–302. [PubMed] [Google Scholar]
  11. Chang H. C. GASTRIC SECRETION IN FEVER AND INFECTIOUS DISEASES. J Clin Invest. 1933 Jan;12(1):155–169. doi: 10.1172/JCI100486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cockcroft D. W., Gault M. H. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41. doi: 10.1159/000180580. [DOI] [PubMed] [Google Scholar]
  13. D'Espine M., Bellido F., Pechère J. C., Auckenthaler R., Rohner P., Lew D., Hirschel B. Serum levels of ciprofloxacin after single oral doses in patients with septicemia. Eur J Clin Microbiol Infect Dis. 1989 Dec;8(12):1019–1023. doi: 10.1007/BF01975162. [DOI] [PubMed] [Google Scholar]
  14. File T. M., Jr, Tan J. S. The use of oral fluoroquinolones in nursing home patients. Drugs Aging. 1992 Jul-Aug;2(4):310–329. doi: 10.2165/00002512-199202040-00005. [DOI] [PubMed] [Google Scholar]
  15. Fillastre J. P., Leroy A., Moulin B., Dhib M., Borsa-Lebas F., Humbert G. Pharmacokinetics of quinolones in renal insufficiency. J Antimicrob Chemother. 1990 Oct;26 (Suppl B):51–60. doi: 10.1093/jac/26.suppl_b.51. [DOI] [PubMed] [Google Scholar]
  16. GILLENWATER J. Y., FROHLICH E. D., KELLER A. D. DIFFERENTIAL EFFECTS OF HEAT ON SPLENIC AND RENAL VASCULAR BEDS. Am J Physiol. 1964 Jul;207:133–136. doi: 10.1152/ajplegacy.1964.207.1.133. [DOI] [PubMed] [Google Scholar]
  17. Ghezzi P., Saccardo B., Villa P., Rossi V., Bianchi M., Dinarello C. A. Role of interleukin-1 in the depression of liver drug metabolism by endotoxin. Infect Immun. 1986 Dec;54(3):837–840. doi: 10.1128/iai.54.3.837-840.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gray J. Treatment of pneumonia in the elderly: pharmacological considerations. Semin Respir Infect. 1990 Dec;5(4):295–302. [PubMed] [Google Scholar]
  19. Heizmann P., Dell D., Eggers H., Gora R. Determination of the new fluoroquinolone fleroxacin and its N-demethyl and N-oxide metabolites in plasma and urine by high-performance liquid chromatography with fluorescence detection. J Chromatogr. 1990 Apr 27;527(1):91–101. doi: 10.1016/s0378-4347(00)82086-1. [DOI] [PubMed] [Google Scholar]
  20. Hooper D. C., Wolfson J. S. Fluoroquinolone antimicrobial agents. N Engl J Med. 1991 Feb 7;324(6):384–394. doi: 10.1056/NEJM199102073240606. [DOI] [PubMed] [Google Scholar]
  21. Lepage J. Y., Caillon J., Malinowsky J. M., Lequerré S., Cozian A., Le Normand Y., Potel G., Drugeon H., Baron D. Pharmacokinetics of norfloxacin in the elderly. Fundam Clin Pharmacol. 1991;5(3):203–208. doi: 10.1111/j.1472-8206.1991.tb00712.x. [DOI] [PubMed] [Google Scholar]
  22. Limberg J., LeBel M., Derendorf H. Evaluation of free tissue concentrations of fleroxacin after oral administration. Pharm Res. 1990 Apr;7(4):422–424. doi: 10.1023/a:1015840027022. [DOI] [PubMed] [Google Scholar]
  23. Lubowski T. J., Nightingale C., Sweeney K., Quintiliani R., Zhi J. Penetration of fleroxacin and ciprofloxacin into skin blister fluid: a comparative study. Antimicrob Agents Chemother. 1992 Mar;36(3):651–655. doi: 10.1128/aac.36.3.651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mackowiak P. A. Influence of fever on pharmacokinetics. Rev Infect Dis. 1989 Sep-Oct;11(5):804–807. [PubMed] [Google Scholar]
  25. Meyers B. R., Wilkinson P. Clinical pharmacokinetics of antibacterial drugs in the elderly. Implications for selection and dosage. Clin Pharmacokinet. 1989 Dec;17(6):385–395. doi: 10.2165/00003088-198917060-00003. [DOI] [PubMed] [Google Scholar]
  26. Montay G., Gaillot J. Pharmacokinetics of fluoroquinolones in hepatic failure. J Antimicrob Chemother. 1990 Oct;26 (Suppl B):61–67. doi: 10.1093/jac/26.suppl_b.61. [DOI] [PubMed] [Google Scholar]
  27. Nakashima M., Kanamaru M., Uematsu T., Takiguchi A., Mizuno A., Itaya T., Kawahara F., Ooie T., Saito S., Uchida H. Clinical pharmacokinetics and tolerance of fleroxacin in healthy male volunteers. J Antimicrob Chemother. 1988 Oct;22 (Suppl 500):133–144. doi: 10.1093/jac/22.supplement_d.133. [DOI] [PubMed] [Google Scholar]
  28. Nightingale C. H. Overview of the pharmacokinetics of fleroxacin. Am J Med. 1993 Mar 22;94(3A):38S–43S. [PubMed] [Google Scholar]
  29. Nilsson-Ehle I., Ljungberg B. Quinolone disposition in the elderly. Practical implications. Drugs Aging. 1991 Jul-Aug;1(4):279–288. doi: 10.2165/00002512-199101040-00004. [DOI] [PubMed] [Google Scholar]
  30. Paganoni R., Herzog C., Braunsteiner A., Hohl P. Fleroxacin: in-vitro activity worldwide against 20,807 clinical isolates and comparison to ciprofloxacin and norfloxacin. J Antimicrob Chemother. 1988 Oct;22 (Suppl 500):3–17. doi: 10.1093/jac/22.supplement_d.3. [DOI] [PubMed] [Google Scholar]
  31. Portmann R., Weidekamm E. Penetration of fleroxacin into human and animal tissues. Chemotherapy. 1992;38(3):145–149. doi: 10.1159/000238954. [DOI] [PubMed] [Google Scholar]
  32. Rohner P., Peebo M., Lew D. P., Auckenthaler R., Pechère J. C. Comparative in-vitro activity of new quinolones against clinical isolates and resistant mutants. J Antimicrob Chemother. 1992 Jan;29(1):41–48. doi: 10.1093/jac/29.1.41. [DOI] [PubMed] [Google Scholar]
  33. Salam Abdullah A., Baggot J. D. Influence of induced disease states on the disposition kinetics of imidocarb in goats. J Vet Pharmacol Ther. 1986 Jun;9(2):192–197. doi: 10.1111/j.1365-2885.1986.tb00029.x. [DOI] [PubMed] [Google Scholar]
  34. Sanders W. E., Jr, Morris J. F., Alessi P., Makris A. T., McCloskey R. V., Trenholme G. M., Iannini P., Bittner M. J. Oral ofloxacin for the treatment of acute bacterial pneumonia: use of a nontraditional protocol to compare experimental therapy with "usual care" in a multicenter clinical trial. Am J Med. 1991 Sep;91(3):261–266. doi: 10.1016/0002-9343(91)90125-h. [DOI] [PubMed] [Google Scholar]
  35. Schentag J. J., Goss T. F. Quinolone pharmacokinetics in the elderly. Am J Med. 1992 Apr 6;92(4A):33S–37S. doi: 10.1016/0002-9343(92)90305-u. [DOI] [PubMed] [Google Scholar]
  36. Schrenzel J., Dayer P., Leemann T., Weidekamm E., Portmann R., Lew D. P. Influence of rifampin on fleroxacin pharmacokinetics. Antimicrob Agents Chemother. 1993 Oct;37(10):2132–2138. doi: 10.1128/aac.37.10.2132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Singlas E., Leroy A., Sultan E., Godin M., Moulin B., Taburet A. M., Dhib M., Fillastre J. P. Disposition of fleroxacin, a new trifluoroquinolone, and its metabolites. Pharmacokinetics in renal failure and influence of haemodialysis. Clin Pharmacokinet. 1990 Jul;19(1):67–79. doi: 10.2165/00003088-199019010-00005. [DOI] [PubMed] [Google Scholar]
  38. Sorgel F., Metz R., Naber K., Seelmann R., Muth P. Pharmacokinetics and body fluid penetration of fleroxacin in healthy volunteers. J Antimicrob Chemother. 1988 Oct;22 (Suppl 500):155–167. doi: 10.1093/jac/22.supplement_d.155. [DOI] [PubMed] [Google Scholar]
  39. Stratton C. Fluoroquinolone antibiotics: properties of the class and individual agents. Clin Ther. 1992 May-Jun;14(3):348–347. [PubMed] [Google Scholar]
  40. Stuck A. E., Frey F. J., Heizmann P., Brandt R., Weidekamm E. Pharmacokinetics and metabolism of intravenous and oral fleroxacin in subjects with normal and impaired renal function and in patients on continuous ambulatory peritoneal dialysis. Antimicrob Agents Chemother. 1989 Mar;33(3):373–381. doi: 10.1128/aac.33.3.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Stuck A. E., Kim D. K., Frey F. J. Fleroxacin clinical pharmacokinetics. Clin Pharmacokinet. 1992 Feb;22(2):116–131. doi: 10.2165/00003088-199222020-00003. [DOI] [PubMed] [Google Scholar]
  42. Sörgel F., Kinzig M. Pharmacokinetics of gyrase inhibitors, Part 2: Renal and hepatic elimination pathways and drug interactions. Am J Med. 1993 Mar 22;94(3A):56S–69S. [PubMed] [Google Scholar]
  43. Sörgel F. Metabolism of gyrase inhibitors. Rev Infect Dis. 1989 Jul-Aug;11 (Suppl 5):S1119–S1129. doi: 10.1093/clinids/11.supplement_5.s1119. [DOI] [PubMed] [Google Scholar]
  44. Taburet A. M., Devillers A., Thomare P., Fillastre J. P., Veyssier P., Singlas E. Disposition of fleroxacin, a new trifluoroquinolone, and its metabolites. Pharmacokinetics in elderly patients. Clin Pharmacokinet. 1990 Jul;19(1):80–88. doi: 10.2165/00003088-199019010-00006. [DOI] [PubMed] [Google Scholar]
  45. Van Miert A. S., Van Gogh H., Wit J. G. The influence of pyrogen induced fever on absorption of sulpha drugs. Vet Rec. 1976 Dec 11;99(24):480–481. doi: 10.1136/vr.99.24.480. [DOI] [PubMed] [Google Scholar]
  46. Weidekamm E. Pharmacokinetics of fleroxacin in renal impairment. Am J Med. 1993 Mar 22;94(3A):70S–74S. [PubMed] [Google Scholar]
  47. Weidekamm E., Portmann R., Partos C., Dell D. Single and multiple dose pharmacokinetics of fleroxacin. J Antimicrob Chemother. 1988 Oct;22 (Suppl 500):145–154. doi: 10.1093/jac/22.supplement_d.145. [DOI] [PubMed] [Google Scholar]
  48. Weidekamm E., Portmann R. Penetration of fleroxacin into body tissues and fluids. Am J Med. 1993 Mar 22;94(3A):75S–80S. [PubMed] [Google Scholar]
  49. Weidekamm E., Portmann R., Suter K., Partos C., Dell D., Lücker P. W. Single- and multiple-dose pharmacokinetics of fleroxacin, a trifluorinated quinolone, in humans. Antimicrob Agents Chemother. 1987 Dec;31(12):1909–1914. doi: 10.1128/aac.31.12.1909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Wolfson J. S., Hooper D. C. Fluoroquinolone antimicrobial agents. Clin Microbiol Rev. 1989 Oct;2(4):378–424. doi: 10.1128/cmr.2.4.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Wolfson J. S., Hooper D. C. Pharmacokinetics of quinolones: newer aspects. Eur J Clin Microbiol Infect Dis. 1991 Apr;10(4):267–274. doi: 10.1007/BF01967000. [DOI] [PubMed] [Google Scholar]
  52. van Miert A. Influence of febrile disease on the pharmacokinetics of veterinary drugs. Ann Rech Vet. 1990;21 (Suppl 1):11S–28S. [PubMed] [Google Scholar]

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

RESOURCES