Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1990 Jan;34(1):58–64. doi: 10.1128/aac.34.1.58

Renal handling of fleroxacin in rabbits, dogs, and humans.

K Shiba 1, A Saito 1, J Shimada 1, S Hori 1, M Kaji 1, T Miyahara 1, H Kusajima 1, S Kaneko 1, S Saito 1, T Ooie 1, et al.
PMCID: PMC171520  PMID: 2109576

Abstract

The renal handling of fleroxacin was studied by renal clearance and stop-flow techniques in rabbits and dogs and by analyzing the pharmacokinetics with and without probenecid in humans. In rabbits the excretion ratios (fleroxacin intrinsic renal clearance/glomerular filtration rate) were greater than unity (2.01) without probenecid and were decreased to a value below unity (0.680) with probenecid. In dogs, on the other hand, the excretion ratios were less than unity (0.608 and 0.456) both without and with probenecid, and so were not affected by probenecid. This fact suggested that fleroxacin was excreted into urine by both glomerular filtration and renal tubular secretion in rabbits, but only by glomerular filtration in dogs, accompanied by partial renal tubular reabsorption in both species; these mechanisms were also supported by stop-flow experiments. In humans probenecid treatment induced increases in the elimination half-life and area under the serum concentration-time curve and decreases in apparent serum clearance, renal clearance, and urinary recovery of fleroxacin. The excretion ratio without probenecid was 1.13, which was significantly decreased to 0.750 with probenecid. These results indicated that both renal tubular secretion and reabsorption contributed to renal excretion of fleroxacin in humans. The contribution of tubular secretion was species dependent and was extensive in rabbits, minimal in dogs, and moderate in humans. Renal tubular reabsorption was commonly found in every species. The long elimination half-life of fleroxacin in humans might be explained by its small total serum clearance and small renal clearance, which are attributed to less tubular secretion and more tubular reabsorption.

Full text

PDF
58

Selected References

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

  1. Barbhaiya R. H., Gerber A. U., Craig W. A., Welling P. G. Influence of urinary pH on the pharmacokinetics of cinoxacin in humans and on antibacterial activity in vitro. Antimicrob Agents Chemother. 1982 Mar;21(3):472–480. doi: 10.1128/aac.21.3.472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Campoli-Richards D. M., Monk J. P., Price A., Benfield P., Todd P. A., Ward A. Ciprofloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1988 Apr;35(4):373–447. doi: 10.2165/00003495-198835040-00003. [DOI] [PubMed] [Google Scholar]
  3. Chin N. X., Brittain D. C., Neu H. C. In vitro activity of Ro 23-6240, a new fluorinated 4-quinolone. Antimicrob Agents Chemother. 1986 Apr;29(4):675–680. doi: 10.1128/aac.29.4.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cunningham R. F., Israili Z. H., Dayton P. G. Clinical pharmacokinetics of probenecid. Clin Pharmacokinet. 1981 Mar-Apr;6(2):135–151. doi: 10.2165/00003088-198106020-00004. [DOI] [PubMed] [Google Scholar]
  5. DISCHE Z., BORENFREUND E. A new spectrophotometric method for the detection and determination of keto sugars and trioses. J Biol Chem. 1951 Oct;192(2):583–587. [PubMed] [Google Scholar]
  6. Hirai K., Aoyama H., Hosaka M., Oomori Y., Niwata Y., Suzue S., Irikura T. In vitro and in vivo antibacterial activity of AM-833, a new quinolone derivative. Antimicrob Agents Chemother. 1986 Jun;29(6):1059–1066. doi: 10.1128/aac.29.6.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Israel K. S., Black H. R., Nelson R. L., Brunson M. K., Nash J. F., Brier G. L., Wolney J. D. Cinoxacin: pharmacokinetics and the effect of probenecid. J Clin Pharmacol. 1978 Oct;18(10):491–499. doi: 10.1002/j.1552-4604.1978.tb01577.x. [DOI] [PubMed] [Google Scholar]
  8. Koike M., Norikura R., Mizojiri K., Sugeno K. Time-dependent elimination of cinoxacin in rats. J Pharm Sci. 1984 Dec;73(12):1697–1700. doi: 10.1002/jps.2600731208. [DOI] [PubMed] [Google Scholar]
  9. Kusajima H., Ishikawa N., Machida M., Uchida H., Irikura T. Pharmacokinetics of a new quinolone, AM-833, in mice, rats, rabbits, dogs, and monkeys. Antimicrob Agents Chemother. 1986 Aug;30(2):304–309. doi: 10.1128/aac.30.2.304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kusajima H., Ooie T., Kawahara F., Uchida H. High-performance liquid chromatographic determination of 6,8-difluoro-1-(2-fluoroethyl)-1,4- dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid and its metabolites in laboratory animals. J Chromatogr. 1986 Aug 22;381(1):137–148. doi: 10.1016/s0378-4347(00)83572-0. [DOI] [PubMed] [Google Scholar]
  11. Manek N., Andrews J. M., Wise R. In vitro activity of Ro 23-6240, a new difluoroquinolone derivative, compared with that of other antimicrobial agents. Antimicrob Agents Chemother. 1986 Aug;30(2):330–332. doi: 10.1128/aac.30.2.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Paton J. H., Reeves D. S. Fluoroquinolone antibiotics. Microbiology, pharmacokinetics and clinical use. Drugs. 1988 Aug;36(2):193–228. doi: 10.2165/00003495-198836020-00004. [DOI] [PubMed] [Google Scholar]
  14. Quay J. F., Childers R. F., Johnson D. W., Nash J. F., Stucky J. F., 2nd Cinoxacin in female mongrel dogs: effect of urine pH on urinary drug excretion and correlation of in vitro characteristics of oral dosage forms with bioavailability. J Pharm Sci. 1979 Feb;68(2):227–232. doi: 10.1002/jps.2600680227. [DOI] [PubMed] [Google Scholar]
  15. Rodriguez N., Madsen P. O., Welling P. G. Influence of probenecid on serum levels and urinary excretion of cinoxacin. Antimicrob Agents Chemother. 1979 Mar;15(3):465–469. doi: 10.1128/aac.15.3.465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Shimada J., Yamaji T., Ueda Y., Uchida H., Kusajima H., Irikura T. Mechanism of renal excretion of AM-715, a new quinolonecarboxylic acid derivative, in rabbits, dogs, and humans. Antimicrob Agents Chemother. 1983 Jan;23(1):1–7. doi: 10.1128/aac.23.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Wise R., Kirkpatrick B., Ashby J., Griggs D. J. Pharmacokinetics and tissue penetration of Ro 23-6240, a new trifluoroquinolone. Antimicrob Agents Chemother. 1987 Feb;31(2):161–163. doi: 10.1128/aac.31.2.161. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES