Clinical Pharmacokinetics

, Volume 29, Supplement 2, pp 62–66 | Cite as

The Effect of Food on the Pharmacokinetics of Zileuton

  • Walid M. Awni
  • John H. Cavanaugh
  • Galen Witt
  • G. Richard Granneman
  • Louise M. Dubé


The present study was undertaken to assess the effect of food on the pharmacokinetic parameters of zileuton. In a nonblinded crossover study, 18 healthy male volunteers who had fasted overnight were randomised to receive a single oral dose of zileuton 600mg in the presence or absence of food consisting of a standardised breakfast on the following morning. The mean zileuton peak plasma concentration (Cmax) increased significantly by 27% after food intake, while the mean area under the plasma concentration versus time curve increased by only 1.4%, a difference that was not statistically significant. The mean time to Cmax was unaffected by the presence of food, as were the other pharmacokinetic parameters assessed.

Overall, the results suggest that food has a relatively small effect on the rate of zileuton absorption compared with the fasting state, while the bioavailability of the drug appears to be unaffected. Thus, it is concluded that it is appropriate to administer zileuton with or without food.


Single Oral Dose Hepatic Blood Flow Zileuton High Performance Liquid Chroma Statistical Analysis System Institute 
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  1. 1.
    Carter GW, Young PR, Albert DH, et al. 5-lipoxygenase inhibitory activity of zileuton. J Pharmacol Exp Ther 1991; 256: 929–37PubMedGoogle Scholar
  2. 2.
    Abraham WM, Ahmed A, Cortes A, et al. The 5-lipoxygenase inhibitor zileuton blocks antigen-induced late airway responses, inflammation and airway hyperresponsiveness in allergic sheep. Eur J Pharmacol 1992; 217: 119–26PubMedCrossRefGoogle Scholar
  3. 3.
    Collawn C, Rubin P, Perez N, et al. Phase II study of the safety and efficacy of a 5-lipoxygenase inhibitor in patients with ulcerative colitis. Am J Gastroenterol 1992; 87: 342–6PubMedGoogle Scholar
  4. 4.
    Hui KP, Taylor IK, Taylor GW, et al. Effect of a 5-lipoxygenase inhibitor on leukotriene generation and airway responses after allergen challenge in asthmatic patients. Thorax 1991; 46: 184–9PubMedCrossRefGoogle Scholar
  5. 5.
    Israel E, Dermarkarian R, Rosenberg M, et al. The effects of a 5-lipoxygenase inhibitor on asthma induced by cold, dry air. N Engl J Med 1990; 323: 1740–4PubMedCrossRefGoogle Scholar
  6. 6.
    Israel E, Rubin P, Kemp JP, et al. The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma. Ann Intern Med 1993; 119: 1059–66PubMedGoogle Scholar
  7. 7.
    Laursen L-S, Naesdal J, Bukhare K, et al. Selective 5-lipoxygenase inhibition in ulcerative colitis. Lancet 1990; 335: 683–5PubMedCrossRefGoogle Scholar
  8. 8.
    Wong SL, Awni WM, Cavanaugh J, et al. The pharmacokinetics of single oral doses of zileuton 200 to 800mg, its enantiomers, and its metabolites, in normal healthy volunteers. Clin Pharmacokinet 29; Suppl. 2: 9–21Google Scholar
  9. 9.
    Granneman GR, Braeckman RA, Erdman KA. Determination of a new 5-lipoxygenase inhibitor, zileuton, and its inactive N-dehydroxylated metabolite in plasma by high performance liquid chromatography. Clin Pharmacokinet 29; Suppl. 2: 1–8Google Scholar
  10. 10.
    SAS Institute. The GLM Procedure. In: SAS/STAT user’s guide, Version 6. 4th ed., volume 2. Cary NC: SAS Institute, 1989: 891–996Google Scholar
  11. 11.
    Locke CS. Use of a more general model for bioavailability studies. Communications in Statistics — Theory and Methods 1990; 19: 3361–73CrossRefGoogle Scholar
  12. 12.
    Winstanley PA, Orme ML’E. The effects of food on drug bioavailability. Br J Clin Pharmacol 1989; 28: 621–8PubMedCrossRefGoogle Scholar
  13. 13.
    Welling PG. Effects of gastrointestinal disease on drug absorption In: Benet LZ, Massod N, Gambertoglio JG, editors. Pharmacokinetic basis for drug treatment. New York: Raven Press, 1984: 29–47Google Scholar
  14. 14.
    Rowland M, Tozer TN. Integration with kinetics. In: Rowland M, Tozer TN. Clinical pharmacokinetics: concepts and applications. Philadelphia: Lea and Febiger, 1989: 177–93Google Scholar

Copyright information

© Adis International Limited 1995

Authors and Affiliations

  • Walid M. Awni
    • 1
  • John H. Cavanaugh
    • 2
  • Galen Witt
    • 3
  • G. Richard Granneman
    • 1
  • Louise M. Dubé
    • 4
  1. 1.Pharmacokinetics and Biopharmaceutics DepartmentAbbott Laboratories, D4PK, AP13AAbbott ParkUSA
  2. 2.Clinical Pharmacology DepartmentAbbott LaboratoriesAbbott ParkUSA
  3. 3.Statistics DepartmentAbbott LaboratoriesAbbott ParkUSA
  4. 4.The Immunoscience VentureAbbott LaboratoriesAbbott ParkUSA

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