Pharmaceutisch Weekblad

, Volume 10, Issue 5, pp 193–199 | Cite as

Pharmacokinetics of nalidixic acid in man: Hydroxylation and glucuronidation

  • T. B. Vree
  • W. J. A. Wijnands
  • A. M. Baars
  • Y. A. Hekster
Original Articles


Nalidixic acid is metabolized by hydroxylation to 7-hydroxymethylnalidixic acid∥ and then by oxidation to 7-carboxynalidixic acid.∥ The half-lives of the two elimination phases of nalidixic acid are 0.75 and 2.5 h. The apparent half-lives of the metabolite 7-hydroxymethylnalidixic acid are 2.5 and 5.5 h. Plasma protein binding of nalidixic acid is 95% and that of 7-hydroxymethylnalidixic acid 65%. The renal clearance of nalidixic acid varies between 2 and 25 ml/min and that of 7-hydroxymethylnalidixic acid between 37 and 162 ml/min. Of nalidixic acid 42% is glucuronidated and 40% hydroxylated. Of the hydroxy metabolite 57% is glucuronidated and 32% excreted unchanged. 7-Carboxynalidixic acid is excreted in the urine and is not glucuronidated. The variations in the glucuronidation/ hydroxylation ratio of nalidixic acid and the glucuronidation/renal excretion ratio of the 7-hydroxymethyl metabolite belong to a normal distribution.


Chromatography, high pressure liquid Clearance Metabolism Nalidixic acid Pharmacokinetics Protein binding 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ferry N, Cuisinaud G, Pozet N, Zech PY, Sassard J. Nalidixic acid kinetics after single and repeated oral doses. Clin Pharmacol Ther 1981;29:695–8.PubMedGoogle Scholar
  2. 2.
    Cuisinaud G, Ferry N, Seccia M, Bernard N, Sassard J. Determination of nalidixic acid and its two major metabolites in human plasma and urine by reversed phase high performance liquid chromatography. J Chromatogr 1980;181:399–406.PubMedGoogle Scholar
  3. 3.
    Cuisinaud G, Ferry N, Pozet N, Zech PY, Sassard J. Nalidixic acid kinetics in renal insufficiency. Br J Clin Pharmacol 1982;14:489–93.PubMedGoogle Scholar
  4. 4.
    Ferry N, Cuisinaud G, Pozet N, Zech PY, Sassard J. Influence du probénécide sur la pharmacocinétique de l'acide nalidixique. Therapie 1982;37:645–9.PubMedGoogle Scholar
  5. 5.
    Ferry N, Cuisinaud G, Sassard J. Pharmacokinetics of nalidixic acid associated with sodium citrate. Biopharm Drug Dispos 1984;5:211–8.PubMedGoogle Scholar
  6. 6.
    McChesney EW, Froelich EJ, Lesher GY, Grain AVR, Rosi D. Absorption, excretion and metabolism of a new antibacterial agent nalidixic acid. Toxicol Appl Pharmacol 1964;6:292–309.Google Scholar
  7. 7.
    Portmann GA, McChesney EW, Stander H, Moore WE. Pharmacokinetic model for nalidixic acid in man. 11. Parameters for absorption, metabolism and elimination. J Pharm Sci 1966;55:72–8.PubMedGoogle Scholar
  8. 8.
    Männistö PT. Pharmacokinetics of nalidixic acid and oxolinic acid in healthy women. Clin Pharmacol Ther 1976;19:37–46.PubMedGoogle Scholar
  9. 9.
    Wijnands WJA, Vree TB, Van Herwaarden CLA. The influence of quinolone derivatives on theophylline clearance. Br J Clin Pharmacol 1986;22:677–83.PubMedGoogle Scholar
  10. 10.
    Wijnands WJA, Vree TB, Van Herwaarden CLA. The effect of the 4-quinolone enoxacin on plasma theophylline concentrations. Pharm Weekbl [Sci] 1986;8:35–40.Google Scholar
  11. 11.
    Metzler CM, Elfring GL, McEwen AJ. A package of computer programs for pharmacokinetic monitoring. Biometrics 1974;572–80.Google Scholar
  12. 12.
    Anonymous. SAS User's guide. Basics 1982 Edition. Cary: SAS Institute Inc., 1982.Google Scholar
  13. 13.
    Shapiro SS, Wilk MB. An analysis of variance test for normality (complete samples). Biometrika 1965;52:591–611.Google Scholar
  14. 14.
    Brühl P, Grundlach G, Wintjes K, Eicher W, Bastian HP. Neue Untersuchungen zur Pharmacokinetik der Nalidixinsäure. Arzneimittelforsch 1973;23:1311–3.PubMedGoogle Scholar
  15. 15.
    Portmann GA, McChesney EW, Stander H, Moore WE. Pharmacokinetic model for nalidixic acid in man. I. Kinetic pathways for hydroxynalidixic acid. J Pharm Sci 1966;55:59–62.PubMedGoogle Scholar
  16. 16.
    Hundt HKL, Barlow EC. Thin-layer Chromatographic method for the quantitative analysis of nalidixic acid in human plasma. J Chromatogr 1981;223:165–72.PubMedGoogle Scholar
  17. 17.
    Sorel RHA, Hulshoff A, Snelleman C. High-performance chromatographic analysis of nalidixic acid and hydroxynalidixic acid in plasma with dynamic anionexchange system. J Chromatogr 1980;221:129–37.PubMedGoogle Scholar
  18. 18.
    Vree TB, Wijnands WJA, Guelen PJM, Baars AM, Hekster YA. Pharmacokinetics, metabolism and renal excretion of quinolones in man. Pharm Weekbl [Sci] 1986;8:29–34.Google Scholar
  19. 19.
    Dickinson RG, Hooper WD, Eadie MJ. pH-Dependent rearrangement of the biosynthetic ester glucuronide of valproic acid to beta-glucuronidase-resistant forms. Drug Metab Dispos 1984;12:247–52.PubMedGoogle Scholar
  20. 20.
    Smith PC, Hasegawa J, Langendijk PNJ, Benet LZ. Stability of acyl glucuronides in blood, plasma and urine. Studies with zomepirac. Drug-Metab Dispos 1985;13:110–2.PubMedGoogle Scholar
  21. 21.
    Eggers NJ, Doust K. Isolation and identification of probenecid acyl glucuronide. J Pharm Pharmacol 1981;33:123–4.PubMedGoogle Scholar
  22. 22.
    Faed M. Properties of acyl glucuronides: implications for studies of the pharmacokinetics and metabolism of acidic drugs. Drug Metab Rev 1984;15:1213–49.PubMedGoogle Scholar
  23. 23.
    Barbeau G, Belanger P-M. Pharmacokinetics of nalidixic acid in old and young volunteers. J Clin Pharmacol 1982;22:490–6.PubMedGoogle Scholar

Copyright information

© Bohn, Scheltema & Holkema 1988

Authors and Affiliations

  • T. B. Vree
    • 1
    • 2
  • W. J. A. Wijnands
    • 3
  • A. M. Baars
    • 1
  • Y. A. Hekster
    • 1
  1. 1.Department of Clinical PharmacySt. Radboud HospitalHB Nijmegenthe Netherlands
  2. 2.Department of AnaesthesiologySt. Radboud HospitalThe Netherlands
  3. 3.Department of Pulmonary DiseasesStichting Deventer ZiekenhuizenAL Deventerthe Netherlands

Personalised recommendations