Advertisement

Pharmaceutisch Weekblad

, Volume 8, Issue 1, pp 29–34 | Cite as

Pharmacokinetics: metabolism and renal excretion of quinolones in man

  • T. B. Vree
  • W. J. A. Wijnands
  • P. J. M. Guelen
  • A. M. Baars
  • Y. A. Hekster
Quinolones in Perspective

Abstract

The quinolones are relatively poorly absorbed from the gastrointestinal tract. The elimination proceeds mainly by renal excretion. The half-life of elimination depends on the molecular structure and varies between 2 and 10 h. Impaired kidney function is expected to increase the half-life of elimination. though this effect is not always observed. Since the 4-oxo-metabolites show a higher renal clearance than the parent drug, renal impairment will result in a cumulation of the metabolites in the body.

Key words

Absorption Kidney failure Metabolism Pharmacokinetics Quinolones Renal excretion 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Cuisinaud G, Ferry N, Pozet N, Zech PY, Sassard J. Nalidixic acid kinetics in renal insufficiency. Br J Clin Pharmacol 1982;14:489–93.Google Scholar
  2. 2.
    Ferry N, Cuisinaud G, Pozet N, Zech PY, Sassard J. Nalidixic kinetics after single and repeated oral doses. Clin Pharmacol Ther 1981;29:695–8.Google Scholar
  3. 3.
    Vree TB, Baars AM, Wijnands WJA. High performance liquid chromatography and preliminary pharmacokinetics of enoxacin and its 4-oxo metabolite in plasma, urine and saliva of man. J Chromatogr 1985;343:449–54.Google Scholar
  4. 4.
    Montay G, Goueffon Y, Roquet F. Absorption, distribution, metabolic fate, and elimination of pefloxacin mesylate in mice, rats, dogs, monkeys and humans. Antimicrob Agents Chemother 1984;25:463–72.Google Scholar
  5. 5.
    Montay G, Tassel JP. Improved high-performance liquid Chromatographic determination of pefloxacin and its metabolite norfloxacin in human plasma and tissue. J Chromatogr 1985;339:214–8.Google Scholar
  6. 6.
    Wolff M, Regnier B, Daldoss C, Nkam M, Vachon F. Penetration of pefloxacin into cerebrospinal fluid of patients with meningitis. Antimicrob Agents Chemother 1984;26:289–91.Google Scholar
  7. 7.
    Eandi M, Viano I, Di Nola 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.Google Scholar
  8. 8.
    Forchetti C, Flammini D, Carlucci G, Cavicchio G, Vaggi L, Bologna M. High-performance liquid chromatography procedure for the quantitation of norfloxacin and metabolites in urine, serum and tissues. J Chromatogr 1984;309:177–82.Google Scholar
  9. 9.
    Ozaki T, Uchida H, Irikura T. Study on the metabolism of AM-715 (norfloxacin) in humans by means of high-performance liquid chromatography. Chemotherapy (Tokyo) 1981;29(suppl 4):128–35.Google Scholar
  10. 10.
    Pauliukonis LT, Musson DG, Bayne WF. Quantitation of norfloxacin, a new antibacterial agent in human plasma and urine by ion-pair reverse-phase chromatography. J Pharm Sci 1984;73:99–102.Google Scholar
  11. 11.
    Sakano T, Masuda S, Amano T. Quantitative analysis of cinoxacin metabolites in human urine. Chemotherapy (Tokyo) 1980;28(suppl 4):139–42.Google Scholar
  12. 12.
    Jehl F, Gallion C, Debs J, Brogard JM, Monteil H, Minck R. High-performance liquid Chromatographic method for determination of ciprofloxacin in biological fluids. J Chromatogr 1985;339:347–57.Google Scholar
  13. 13.
    Joos B, Ledergerber B, Flepp F, Bettex J-D, Lüthy R, Siegenthaler W. Comparison of high-pressure liquid chromatography and bioassay for determination of ciprofloxacin in serum and urine. Antimicrob Agents Chemother 1985;27:353–6.Google Scholar
  14. 14.
    Weber A, Chaffin D, Smith A, Opheim KE. Quantitation of ciprofloxacin in body fluids by high-pressure liquid chromatography. Antimicrob Agents Chemother 1985;27:531–4.Google Scholar
  15. 15.
    Smethurst AM, Mann WC. Determination by high performance liquid chromatography of pipemidic acid in human serum and urine. J Chromatogr 1983;274:421–7.Google Scholar
  16. 16.
    Black HR, Israel KS, Wolen RL, et al. Pharmacology of cinoxacin in humans. Antimicrob Agents Chemother 1979;15:165–70.Google Scholar
  17. 17.
    Ledergerber B, Bettex JD, Joos B, Flepp M, Lüthy R. Effect of standard breakfast on drug absorption and multiple dose pharmacokinetics of ciprofloxacin. Antimicrob Agents Chemother 1985;27:350–2.Google Scholar
  18. 18.
    Israel KS, Black HR, Nelson RL, et al. Cinoxacin: pharmacokinetics and the effect of probenecid. J Antimicrob Chemother 1981;8:447–57.Google Scholar
  19. 19.
    Rodriguez N, Madsen PO, Welling PG. Influence of probenecid on serum levels and urinary excretion of cinoxacin. Antimicrob Agents Chemother 1979;15:465–9.Google Scholar
  20. 20.
    Sisca TS. Cinoxacin: a review. Drugs 1983;25:546–69.Google Scholar
  21. 21.
    Shimada J, Yamaji T, Ueda Y, Uchida H, Kusajima H, Irikura T. Mechanism of renal excretion of AM-715 (norfloxacin), a new quinolonecarboxylic acid derivative, in rabbits, dogs and humans. Antimicrob Agents Chemother 1983;23:1–7.Google Scholar
  22. 22.
    Janssen TJ, Wijnands WJA, Vree TB, et al. Kinetiek en behandeling van drie doseringen met carbamazepine (Tegretol®). TGO/JDR 1983;8:1707–17.Google Scholar
  23. 23.
    Vree TB, Hekster YA, Tijhuis MW. Metabolism of sulfonamides. Antibiot Chemother 1985;34:5–65.Google Scholar
  24. 24.
    Brogard JM, Comte F, Lavillaureix J. Comparative pharmacokinetic profiles of cinoxacin and pipemidic acid in humans. Eur J Drug Metab Pharmacokinet 1983;8:251–9.Google Scholar
  25. 25.
    Männistö P, Solkinen A, Mäntylä R, et al. Pharmaco-kinetics of pipemidic acid in healthy middle-aged volunteers and elderly patients with renal insufficiency. Xenobiotica 1984;14:339–47.Google Scholar
  26. 26.
    Brogard JM, Jehl F, Arnaud JP, et al. Ciprofloxacine: évaluation de son élimination biliaire chez l'homme. Schweiz Med Wochenschr 1985;115:448–53.Google Scholar
  27. 27.
    Eskens GTF, Goudkuil J. Informatie over geneesmiddelen: Pipram®. TGO/JDR 1983;8:1743–5.Google Scholar
  28. 28.
    Klinge E, Männistö PT, Mäntylä R, Mattila J, Hänninen U. Single- and multiple-dose pharmacokinetics of pipemidic acid in normal volunteers. Antimicrob Agents Chemother 1984;526:69–73.Google Scholar
  29. 29.
    Wise R, Lockley R, Dent J, Webberly M. Pharmaco-kinetics and tissue penetration of enoxacin. Antimicrob Agents Chemother 1984;26:17–9.Google Scholar
  30. 30.
    Wolf R, Eberl R, Dunky A, et al. The clinical pharmacokinetics and tolerance of enoxacin in healthy volunteers. J Antimicrob Chemother 1984;14(suppl C):63–9.Google Scholar
  31. 31.
    Nakano H, Nihira H, Kamiya A, Hori R. Influence of renal impairment on multiple-dose pharmacokinetics of ofloxacin. In: Ofloxacin. Selected proceedings of the 24th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington DC, October 8–10, 1984. Amsterdam —Tokyo: Excerpta Medica 1985:63–8.Google Scholar
  32. 32.
    Admani ZN, Wise R, Weston D, Crump B. The pharmacokinetics and tissue penetration of norfloxacin. J Antimicrob Chemother 1984;13:87–92.Google Scholar
  33. 33.
    Nakamura R, Yamaguchi T, Sekine Y, Hashimoto M. Determination of a new antibacterial agent (AT-2266) and its metabolites in plasma and urine by high performance liquid chromatography. J Chromatogr 1983;278:321–8.Google Scholar
  34. 34.
    Swanson BN, Boppana VK, Vlasses PH, Rotmensch HH, Ferguson RK. Norfloxacin disposition after sequentially increasing oral doses. Antimicrob Agents Chemother 1983;23:284–8.Google Scholar
  35. 35.
    Barre J, Houin G, Tillement JP. Dose-dependent pharmacokinetic study of pefloxacin, a new antibacterial agent, in humans. J Pharm Sci 1984;73:1379–82.Google Scholar
  36. 36.
    Aronoff GE, Kenner CH, Sloan RS, Pottratz ST. Multiple dose ciprofloxacin kinetics in normal subjects. Clin Pharmacol Ther 1984;36:384–8.Google Scholar
  37. 37.
    Crump B, Wise R, Dent J. Pharmacokinetics and tissue penetration of ciprofloxacin. Antimicrob Agents Chemother 1983;24:784–6.Google Scholar
  38. 38.
    Gonzalez MA, Uribe F, Moisen SD, et al. Multiple-dose pharmacokinetics and safety of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother 1984;26:741–4.Google Scholar
  39. 39.
    Höffler D, Dalhoff A, Gau W, Beermann D, Michl A. Dose- and sex-independent disposition of ciprofloxacin. Eur J Clin Microbiol 1984;3:363–6.Google Scholar
  40. 40.
    Wise R, Lockley RM, Webberly M, Dent J. Pharmaco-kinetics of intravenously administered ciprofloxacin. Antimicrob Agents Chemother 1984;26:208–10.Google Scholar
  41. 41.
    Walenkamp GHIM, Vree TB. Treatment of a patient with impaired renal function with gentamicin-PMMA-beads. Arch Orthop Trauma Surg 1981;99:137–41.Google Scholar
  42. 42.
    Hughes PJ, Webb DB, Asscher AW. Pharmacokinetics of norfloxacin (MK366) in patients with impaired kidney function — some preliminary results. J Antimicrob Chemother 1984;13 (suppl B):55–7.Google Scholar
  43. 43.
    Szwed JJ, Brannon DE, Sloan RS, Luft FC. Pharmaco-kinetics of cinoxacin in patients with renal failure. J Antimicrob Chemother 1978;8:451–4.Google Scholar
  44. 44.
    Ohkawa M, Sugata T, Sawaki M, Okasho A, Kuroda K, Yamada H. Pharmacokinetics of cinoxacin in normal volunteers and patients with impaired renal function. J Antimicrob Chemother 1981;8:447–51.Google Scholar
  45. 45.
    Brumfitt W, Franklin I, Grady D, Hamilton-Miller JMT, 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;26:757–61.Google Scholar
  46. 46.
    Cofsky RD, Du Bouchet L, Landesman SH. Recovery of norfloxacin in feces after administration of a single oral dose to human volunteers. Antimicrob Agents Chemother 1984;26:110–1.Google Scholar
  47. 47.
    Wingerder W, Graefe K-H, Gau W, Föster D, Beermann D, Schacht P. Pharmacokinetics of ciprofloxacin after oral and intravenous administration in healthy volunteers. Eur J Clin Microbiol 1984;3:355–9.Google Scholar
  48. 48.
    Barbeau G, Belanger P-M. Pharmacokinetics of nalidixic acid in old and young volunteers. J Clin Pharmacol 1982;22:490–6.Google Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1986

Authors and Affiliations

  • T. B. Vree
    • 1
    • 4
  • W. J. A. Wijnands
    • 2
  • P. J. M. Guelen
    • 3
  • A. M. Baars
    • 1
  • Y. A. Hekster
    • 1
  1. 1.Department of Clinical PharmacySt. Radboud HospitalHB NijmegenThe Netherlands
  2. 2.Department of Pulmonary DiseasesSt. Radboud HospitalHB NijmegenThe Netherlands
  3. 3.Farma ResearchNV NijmegenThe Netherlands
  4. 4.Department of AnaesthesiologySt. Radboud HospitalHB NijmegenThe Netherlands

Personalised recommendations

Cite article

Buy options