Pharmaceutisch Weekblad

, Volume 9, Supplement 1, pp S16–S22 | Cite as

Pharmacokinetics of the newer fluoroquinolones

  • J. R. B. J. Brouwers


A large number of pharmacokinetic studies have been carried out using 4-quinolones in order to estimate total and renal clearance, to examine tissue penetration, to establish suitable dosage regimens and to determine the influence of kidney and liver impairment on the pharmacokinetic behaviour.

Although the quinolones are poorly water soluble over the physiological pH range (6–8) they are well absorbed following oral administration. Ofloxacin is almost completely absorbed and ciprofloxacin has been shown to have an absolute bioavailability of 0.70. Plasma protein binding varies greatly from quinolone to quinolone ranging from about 10% in the case of norfloxacin to more than 90% in the case of nalidixic acid. Penetration of the quinolones into the prostate is generally good Most quinolones, too, have been shown to penetrate blister fluid rapidly and this model has proved useful in distribution studies. Some quinolones, like ofloxacin, are excreted largely unchanged while others like pefloxacin and acrosoxacin, are almost completely metabolized. Conjugation to very water-soluble glucuronides is not common although other types of metabolites have been shown. Little information appears to have been published on the effect of liver disease on the metabolism of the quinolones. This must be an important consideration for this type of drugs which are subject to hepatic transformation. The pharmacokinetic behaviour of quinolones in patients with impaired renal function has been extensively studied. The interaction of food on the absorption does not seem to be great, there is however evidence of a drug interaction between theophylline and some of the newer quinolones. Sucralfate and antacids containing Mg2+ or (and) Al3+ -ions can markedly impair the absorption of quinolone antibiotics.

Key words

Acrosoxacin Ciprofloxacin Enoxacin Fleroxacin Norfloxacin Ofloxacin Pefloxacin Pharmacokinetics 


  1. 1.
    Groeneveld AJN, Brouwers JRBJ. Quantitative determination of ofloxacin, ciprofloxacin, norfloxacin and pefloxacin in serum by HPLC. Pharm Weekbl [Sci] 1986;8:79–84.Google Scholar
  2. 2.
    Schönfeld W, Knöller J, Bremm KD, Dahlhoff A, Weber B, König W. Determination of ciprofloxacin, norfloxacin and ofloxacin by HPLC. Zbl Bakt Hyg 1986;A261:338–44.Google Scholar
  3. 3.
    Jack DB. Recent advances in pharmaceutical chemistry. The 4-quinolone antibiotics. J Clin Hosp Pharm 1986;11:75–93.PubMedGoogle Scholar
  4. 4.
    Holmes B, Brogden RN, Richards DM. Norfloxacin. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic use. Drugs 1985;30:482–513.PubMedGoogle Scholar
  5. 5.
    Vree TB, Wijnands WJA, Guelen PJM, Baars AM, Hekster YA. Pharmacokinetics, metabolism and renal secretion of quinolones in man. Pharm Weekbl [Sci] 1986;8:29–34.Google Scholar
  6. 6.
    Wolf R, Rudolf E, Dunkey A et al. The clinical pharmacokinetics and tolerance of enoxacin in healthy volunteers. J Antimicrob Chemother 1984;14 Suppl C:63–9.PubMedGoogle Scholar
  7. 7.
    Enoxacin: Zusamenfassung der Forschungsergebnisse. Parke Davis Comp Berlin 1986:14.Google Scholar
  8. 8.
    Wise R, Lister D, McNulty CAM, Griggs D, Andrews JM. The comparative pharmacokinetics of five quinolones. J Antimicrob Chemother 1986;18 Suppl D:71–81.PubMedGoogle Scholar
  9. 9.
    Brun Buisson C, Wolff M, Garaud JJ. Pharmacocinétique des nouvelles quinolones. In: “Les nouvelles quinolones”, Ed. JJ Pocidalo, F Vachon, B Regnier. Amette Publications Paris 1985:151–9.Google Scholar
  10. 10.
    Weidekamm E, Stoeckel K, Dell D. Single dose pharmacokinetic of the new fluoroquinolones Ro 23-6240 (AM 833) in man (abstract). Int Symp New Quinolones Geneva Switserland July 17–19. Abstractbook 1986:83.Google Scholar
  11. 11.
    Singlas E, Taburet AM. Pharmacokinétique clinique des nouvelles quinolones. In: “Les nouvelles quinolones”, Ed. JJ Pocidalo, F Vachon, B Regnier. Arnette Publications Paris 1985:83–103.Google Scholar
  12. 12.
    Drusano GL, Plaisance KI, Forest A, Standifort HC. Dose ranging study and constant infusion evaluation of ciprofloxacin. Antimicrob Agents Chemother 1986;30:440–3.PubMedGoogle Scholar
  13. 13.
    Bergan T, Thorsteinsson SB, Solberg R, Bjonskau L, Kolstad I, Johnsen S. Pharmacokinetics of ciprofloxacin: intravenous and increasing oral doses. Am J Med 1987;82 (4A):97–103PubMedGoogle Scholar
  14. 14.
    Frydman AM, Le Roux Y, Lefebvre MA, Djebbar F, Foutillan JB, Gaillot J. Pharmacokinetics of pefloxacin after repeated intravenous and oral administration (400 mg bid) in young healthy volunteers. J Antimicrob Chemother 1986;17 Suppl B:65–79.Google Scholar
  15. 15.
    Monk JP, Campoli-Richards DM. Ofloxacin, a review of its antimicrobial activity, pharmacokinetic properties and therapeutic use. Drugs 1987, 33:346–91.PubMedGoogle Scholar
  16. 16.
    Ro 23-6240 (AM 833) Long acting fluoroquinolones (oral broad spectrum antibacterial agent) Investigational Drug Brochure. Hoffmann-La Roche & Co Ltd Basle Switserland Dec 1986.Google Scholar
  17. 17.
    Rubenstein E, Seger S. Drug interactions of ciprofloxacin with other non-antibiotic agents. Am J Med 1987;82 (4A):119–24.PubMedGoogle Scholar
  18. 18.
    Schentag JJ, Sedman AJ, Wilton JH et al. Interactions between enoxacin, ranitidine and antacids. (Abstractbook p. 119, nr.256) Third European Congress of Clinical Microbiology. 11/14 May 1987. The Hague, NL.Google Scholar
  19. 19.
    Wise R, Lockly R, Webberly M, Adhami ZN. The pharmacokinetics and tissue penetration of enoxacin and norfloxacin. J Antimicrob Chemother 1984;14 Suppl C:75–81.Google Scholar
  20. 20.
    Lockly R, Wise R, Dent J. The pharmacokinetics and tissue penetration of ofloxacin. J. Antimicrob Chemother 1984;14:647–52.PubMedGoogle Scholar
  21. 21.
    Dellamonica P, Bernard E, Etesse H, Garrafto R. The diffusion of pefloxacin into bone and the treatment of osteomyelitis. J Antimicrob Chemother 1986;17 Suppl B:93–102.Google Scholar
  22. 22.
    Tanimura H, Tominaga S, Rai F, Matsumoto H. Transfer of ciprofloxacin to bile and determination of biliary metabolites in humans. Arzneimittelforsch 1986;36:1417–20.PubMedGoogle Scholar
  23. 23.
    Borner K, Lode H, Höffken G. Renal elimination of sulfociprofloxacin a new metabolite of ciprofloxacin. Eur J Clin Microbiol 1986;5:476.PubMedGoogle Scholar
  24. 24.
    Borner K, Lode H. Biotransformation von ausgewählten Gyrasehemmern. Infection 1986;14 Suppl 1:54–9.Google Scholar
  25. 25.
    Bergan T. Dosage regimens of quinolones in reduced renal function. Quinolones Bulletin 1986;2:7–10.Google Scholar
  26. 26.
    Webb DS, Roberts DE, Williams JD, Asscher AW. Pharmacokinetics in healthy volunteers and patients with impaired kidney function. J Antimicrob Chemother 1986;18 Suppl D:83–7.Google Scholar
  27. 27.
    Fleming LW, Stewart WK, Moreland TA, Scott-AC. Pharmacokinetic studies on two day oral ciprofloxacin administration in patients on continuous ambulatory peritoneal dialysis (CAPD). Abstractbook p. 112, nr. 242. Third European Congress of Clinical Microbiology. 11/14 May 1987. The Hague, NL Abstract (nr:242).Google Scholar
  28. 28.
    Danan G, Montay G, Cunci R, Erlinger S. Pefloxacin kinetics in cirrhosis. Clin Pharmacol Ther 1985;38:439–42.PubMedGoogle Scholar
  29. 29.
    Eandi M. Viano I, DiNola F, Leone L, Genazzani E. Pharmacokinetics of norfloxacin in healthy volunteers and patients with renal and hepatic damage. Eur J Clin Microbiol 1983;2:253–9.PubMedGoogle Scholar

Copyright information

© Bohn, Scheltema & Holkema 1987

Authors and Affiliations

  • J. R. B. J. Brouwers
    • 1
  1. 1.Department of Clinical Pharmacy and PharmacokineticsGeneral Hospital De TjongerschansMA HeerenveenThe Netherlands

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