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. 1992 Oct;36(10):2286–2292. doi: 10.1128/aac.36.10.2286

Pharmacokinetics of 18F-labeled fleroxacin in rabbits with Escherichia coli infections, studied with positron emission tomography.

A J Fischman 1, E Livni 1, J Babich 1, N M Alpert 1, Y Y Liu 1, E Thom 1, R Cleeland 1, B L Prosser 1, R J Callahan 1, J A Correia 1, et al.
PMCID: PMC245491  PMID: 1444310

Abstract

18F-labeled fleroxacin was used to measure the pharmacokinetics of fleroxacin in healthy and infected animals by positron emission tomography (PET) and tissue radioactivity measurements. In all experiments, a pharmacological dose of unlabeled drug (10 mg/kg) was coinjected with the tracer. The pharmacokinetics of [18F]fleroxacin was measured in groups of healthy mice (n = six per group) at 10, 30, 60, and 120 min after injection and in groups of rats with Escherichia coli thigh infections (n = six per group) at 60 and 120 min after injection by radioactivity measurements in excised tissues. In healthy rabbits (n = 4) and in rabbits with E. coli thigh infections (n = 4), tissue concentrations of drug were determined by serial PET imaging over 2 h; after the final image was acquired, animals were sacrificed and concentrations measured by PET were compared with the results of tissue radioactivity measurements. In all three species, there was rapid equilibration of [18F]fleroxacin to significant concentrations in most peripheral organs; low concentrations of drug were detected in the brain. Accumulations of radiolabeled drug in infected and healthy thigh muscles were similar. Peak concentrations of drug of more than three times the MIC for 90% of members of the family Enterobacteriaceae (greater than 100-fold for most organisms) were achieved in all tissues except brain and remained above this level for more than 2 h. Especially high peak concentrations were achieved in the kidney (greater than 75 micrograms/g), liver (greater than 50 micrograms/g), blood (greater than 25 micrograms/g), and bone and lung (greater than 10 micrograms/g).Since the MICs for 90% of all Enterobacteriaceae are <2 micrograms/ml, fleroxacin should be particularly useful in treating gram-negative infections affecting these tissues. In contrast, the low concentration of drug delivered to the brain should limit the toxicity of the drug for the central nervous system.

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Selected References

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  1. Awni W. M., Maloney J. A., Heim-Duthoy K. L. Liquid-chromatographic determination of fleroxacin in serum and urine. Clin Chem. 1988 Nov;34(11):2330–2332. [PubMed] [Google Scholar]
  2. Bednarczyk E. M., Green J. A., Nelson A. D., Leisure G. A., Little D., Adler L. P., Berridge M. S., Panacek E. A., Miraldi F. D. Comparison of the effect of temafloxacin, ciprofloxacin, or placebo on cerebral blood flow, glucose, and oxygen metabolism in healthy subjects by means of positron emission tomography. Clin Pharmacol Ther. 1991 Aug;50(2):165–171. doi: 10.1038/clpt.1991.121. [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. Fischman A. J., Alpert N. M., Livni E., Ray S., Sinclair I., Elmaleh D. R., Weiss S., Correia J. A., Webb D., Liss R. Pharmacokinetics of 18F-labeled fluconazole in rabbits with candidal infections studied with positron emission tomography. J Pharmacol Exp Ther. 1991 Dec;259(3):1351–1359. [PubMed] [Google Scholar]
  5. Gardner S. F., Green J. A., Bednarczyk E. M., Nelson A. D., Leisure G., Miraldi F. An assessment of cerebral blood flow and metabolism after fleroxacin therapy. J Clin Pharmacol. 1991 Feb;31(2):151–157. doi: 10.1002/j.1552-4604.1991.tb03699.x. [DOI] [PubMed] [Google Scholar]
  6. Gasser T. C., Graversen P. H., Madsen P. O. Fleroxacin (Ro 23-6240) distribution in canine prostatic tissue and fluids. Antimicrob Agents Chemother. 1987 Jul;31(7):1010–1013. doi: 10.1128/aac.31.7.1010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hayton W. L., Vlahov V., Bacracheva N., Viachki I., Portmann R., Muirhead G., Stoeckel K., Weidekamm E. Pharmacokinetics and biliary concentrations of fleroxacin in cholecystectomized patients. Antimicrob Agents Chemother. 1990 Dec;34(12):2375–2380. doi: 10.1128/aac.34.12.2375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Jynge P., Skjetne T., Gribbestad I., Kleinbloesem C. H., Hoogkamer H. F., Antonsen O., Krane J., Bakøy O. E., Furuheim K. M., Nilsen O. G. In vivo tissue pharmacokinetics by fluorine magnetic resonance spectroscopy: a study of liver and muscle disposition of fleroxacin in humans. Clin Pharmacol Ther. 1990 Nov;48(5):481–489. doi: 10.1038/clpt.1990.183. [DOI] [PubMed] [Google Scholar]
  11. Kees F., Naber K. G., Schumacher H., Grobecker H. Penetration of fleroxacin into prostatic secretion and prostatic adenoma tissue. Chemotherapy. 1988;34(6):437–443. doi: 10.1159/000238605. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Leibovitz E., Keren G., Shabtai M., Barzilai A., Rubinstein E. The pharmacokinetics and therapeutic efficacy of fleroxacin and pefloxacin in a rat abscess model. J Antimicrob Chemother. 1989 Sep;24(3):375–385. doi: 10.1093/jac/24.3.375. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Panneton A. C., Bergeron M. G., LeBel M. Pharmacokinetics and tissue penetration of fleroxacin after single and multiple 400- and 800-mg-dosage regimens. Antimicrob Agents Chemother. 1988 Oct;32(10):1515–1520. doi: 10.1128/aac.32.10.1515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Portmann R., Hansz C., Stiglmayer R., Weidekamm E. Fleroxacin concentrations in myometrium, ovary and fallopian tube. J Antimicrob Chemother. 1989 Apr;23(4):662–664. doi: 10.1093/jac/23.4.662. [DOI] [PubMed] [Google Scholar]
  19. Rota Kops E., Herzog H., Schmid A., Holte S., Feinendegen L. E. Performance characteristics of an eight-ring whole body PET scanner. J Comput Assist Tomogr. 1990 May-Jun;14(3):437–445. doi: 10.1097/00004728-199005000-00022. [DOI] [PubMed] [Google Scholar]
  20. Sörgel F., Seelmann R., Naber K., Metz R., Muth P. Metabolism of fleroxacin in man. J Antimicrob Chemother. 1988 Oct;22 (Suppl 500):169–178. doi: 10.1093/jac/22.supplement_d.169. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Wise R., Honeybourne D., Andrews J. M., Ashby J. P. The penetration of fleroxacin into bronchial mucosa. J Antimicrob Chemother. 1988 Aug;22(2):203–206. doi: 10.1093/jac/22.2.203. [DOI] [PubMed] [Google Scholar]
  23. 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]

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