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. 1996 Mar;40(3):575–580. doi: 10.1128/aac.40.3.575

Factors influencing elimination and distribution of fleroxacin: metaanalysis of individual data from 10 pharmacokinetic studies.

B G Reigner 1, H A Welker 1
PMCID: PMC163160  PMID: 8851573

Abstract

A metaanalysis was conducted on data from 172 subjects (healthy volunteers and uninfected patients) included in 10 pharmacokinetic studies of fleroxacin after oral administration. The objectives of this analysis were (i) to estimate the typical values of two key pharmacokinetic parameters, clearance over systemic availability (CL/F) and volume of distribution over systemic availability (V/F), after the administration of therapeutic doses and (ii) to study qualitatively and quantitatively the factors which influence the elimination and distribution of fleroxacin. The main pharmacokinetic parameters, CL/F and V/F, were analyzed separately by a standard two-stage approach. The covariates investigated were predicted creatinine clearance (CLCR), age, gender, body surface area, body weight, and lean body weight (LBW). The predicted CL/F and V/F were 83.5 ml/min and 101 liters, respectively, for a typical male subject (CLCR, 70 ml/min; LBW, 54 kg; age, 54 years). Modeling of CL/F indicated that this parameter increases linearly with CLCR, decreases linearly with age, and is 10.8 ml/min lower in females than in males. The best model for V/F showed a linear increase with LBW and a linear decrease with age. V/F was found to be 20.4 liters greater in males than in females. In conclusion, this metaanalysis has shown that CLCR, age, and gender influence the elimination of fleroxacin from the body, whereas V/F is influenced by LBW, age, and gender.

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Selected References

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  1. 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]
  2. 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]
  3. De Lepeleire I., Van Hecken A., Verbesselt R., Tjandra-Maga T. B., De Schepper P. J. Comparative oral pharmacokinetics of fleroxacin and pefloxacin. J Antimicrob Chemother. 1988 Aug;22(2):197–202. doi: 10.1093/jac/22.2.197. [DOI] [PubMed] [Google Scholar]
  4. Hallynck T. H., Soep H. H., Thomis J. A., Boelaert J., Daneels R., Dettli L. Should clearance be normalised to body surface or to lean body mass? Br J Clin Pharmacol. 1981 May;11(5):523–526. doi: 10.1111/j.1365-2125.1981.tb01163.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. 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]
  8. Novak L. P. Aging, total body potassium, fat-free mass, and cell mass in males and females between ages 18 and 85 years. J Gerontol. 1972 Oct;27(4):438–443. doi: 10.1093/geronj/27.4.438. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Schrenzel J., Cerruti F., Herrmann M., Leemann T., Weidekamm E., Portmann R., Hirschel B., Lew D. P. Single-dose pharmacokinetics of oral fleroxacin in bacteremic patients. Antimicrob Agents Chemother. 1994 Jun;38(6):1219–1224. doi: 10.1128/aac.38.6.1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Sheiner L. B. Analysis of pharmacokinetic data using parametric models. III. Hypothesis tests and confidence intervals. J Pharmacokinet Biopharm. 1986 Oct;14(5):539–555. doi: 10.1007/BF01059660. [DOI] [PubMed] [Google Scholar]
  13. Sheiner L. B., Rosenberg B., Marathe V. V. Estimation of population characteristics of pharmacokinetic parameters from routine clinical data. J Pharmacokinet Biopharm. 1977 Oct;5(5):445–479. doi: 10.1007/BF01061728. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Soons P. A., Grib C., Breimer D. D., Kirch W. Effects of acute febrile infectious diseases on the oral pharmacokinetics and effects of nitrendipine enantiomers and of bisoprolol. Clin Pharmacokinet. 1992 Sep;23(3):238–248. doi: 10.2165/00003088-199223030-00006. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Steimer J. L., Mallet A., Golmard J. L., Boisvieux J. F. Alternative approaches to estimation of population pharmacokinetic parameters: comparison with the nonlinear mixed-effect model. Drug Metab Rev. 1984;15(1-2):265–292. doi: 10.3109/03602538409015066. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. 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]
  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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