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. 1988 Oct;32(10):1515–1520. doi: 10.1128/aac.32.10.1515

Pharmacokinetics and tissue penetration of fleroxacin after single and multiple 400- and 800-mg-dosage regimens.

A C Panneton 1, M G Bergeron 1, M LeBel 1
PMCID: PMC175910  PMID: 3142338

Abstract

The pharmacokinetics and suction-induced blister fluid penetration of fleroxacin following single and multiple (every 24 h for 5 days) oral administration of 400- and 800-mg-dosage regimens were studied in 12 young male volunteers. Plasma and urine samples up to 72 h were assayed by high-pressure liquid chromatography. The peak levels of fleroxacin in plasma were significantly higher after multiple dosing of 800 mg (14.3 versus 8.2 micrograms/ml; P less than 0.01) but not after the last 400-mg dose (6.7 versus 5.0 micrograms/ml). Increased elimination half-life occurred after multiple dosing of 800 mg, from 13.45 +/- 2.94 to 15.60 +/- 3.16 h (P less than 0.05). Mean peak concentrations in blister fluid were significantly different when the first (3.7 +/- 0.8 and 7.7 +/- 1.8 micrograms/ml for 400 and 800 mg, respectively) and last (5.7 +/- 0.9 and 12.3 +/- 2.1 micrograms/ml for 400 and 800 mg, respectively) doses were compared (P less than 0.01). The percentage of blister fluid (BF) penetration (AUCBF/AUCplasma, where AUC is area under the concentration-time curve) yielded values greater than 100% (range, 113.7 to 132.6%). After multiple administration of 800 mg, fleroxacin was cleared from the body more slowly: from 98.80 ml/min after a single dose to 77.72 ml/min following 800 mg every 24 h (P less than 0.01). Saturation of apparent nonrenal clearance is suggested to explain this difference. Fleroxacin was well tolerated by the volunteers.

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Selected References

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

  1. Boxenbaum H. G., Riegelman S., Elashoff R. M. Statistical estimations in pharmacokinetics. J Pharmacokinet Biopharm. 1974 Apr;2(2):123–148. doi: 10.1007/BF01061504. [DOI] [PubMed] [Google Scholar]
  2. Brumfitt W., Franklin I., Grady D., Hamilton-Miller J. M., Iliffe A. Changes in the pharmacokinetics of ciprofloxacin and fecal flora during administration of a 7-day course to human volunteers. Antimicrob Agents Chemother. 1984 Nov;26(5):757–761. doi: 10.1128/aac.26.5.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dudley M. N., Ericson J., Zinner S. H. Effect of dose on serum pharmacokinetics of intravenous ciprofloxacin with identification and characterization of extravascular compartments using noncompartmental and compartmental pharmacokinetic models. Antimicrob Agents Chemother. 1987 Nov;31(11):1782–1786. doi: 10.1128/aac.31.11.1782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gibaldi M., Weintraub H. Some considerations as to the determination and significance of biologic half-life. J Pharm Sci. 1971 Apr;60(4):624–626. doi: 10.1002/jps.2600600430. [DOI] [PubMed] [Google Scholar]
  5. Gonzalez M. A., Uribe F., Moisen S. D., Fuster A. P., Selen A., Welling P. G., Painter B. Multiple-dose pharmacokinetics and safety of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother. 1984 Nov;26(5):741–744. doi: 10.1128/aac.26.5.741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Le Blanc P. P., Dumas J. Calcul des valeurs initiales des paramètres pharmacocinétiques à l'aide d'un calculateur programmable. Therapie. 1983 Jan-Feb;38(1):21–26. [PubMed] [Google Scholar]
  7. LeBel M., Vallée F., Bergeron M. G. Tissue penetration of ciprofloxacin after single and multiple doses. Antimicrob Agents Chemother. 1986 Mar;29(3):501–505. doi: 10.1128/aac.29.3.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Perrier D., Mayersohn M. Noncompartmental determination of the steady-state volume of distribution for any mode of administration. J Pharm Sci. 1982 Mar;71(3):372–373. doi: 10.1002/jps.2600710332. [DOI] [PubMed] [Google Scholar]
  9. Smith I. L., Schentag J. J. Noncompartmental determination of the steady-state volume of distribution during multiple dosing. J Pharm Sci. 1984 Feb;73(2):281–282. doi: 10.1002/jps.2600730239. [DOI] [PubMed] [Google Scholar]
  10. Timm U., Wall M., Dell D. A new approach for dealing with the stability of drugs in biological fluids. J Pharm Sci. 1985 Sep;74(9):972–977. doi: 10.1002/jps.2600740913. [DOI] [PubMed] [Google Scholar]
  11. Verbist L. Comparative in-vitro activity of Ro 23-6240, a new trifluorinated quinolone. J Antimicrob Chemother. 1987 Sep;20(3):363–372. doi: 10.1093/jac/20.3.363. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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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