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The Effect of Mild or Moderate Hepatic Impairment (Cirrhosis) on the Pharmacokinetics of Zileuton

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Summary

The pharmacokinetics of zileuton and its R(+) and S(−) glucuronide metabolites were determined after single and multiple (400mg every 8 hours) oral dose administration in healthy subjects (n=5) and patients with mild or moderate hepatic impairment (cirrhosis; n=8). The clearance of total zileuton (unbound plus bound to plasma proteins) in patients with hepatic impairment (approximately 350 ml/min) was approximately half that in healthy subjects (approximately 670 ml/min), with similar values in patients with mild or moderate cirrhosis. However, the clearance of unbound zileuton in patients with moderate hepatic impairment was nearly half that in patients with mild hepatic impairment, and one quarter that in healthy subjects. On the basis of these findings, it may be necessary to reduce the dose in patients with impaired hepatic function to maintain levels similar to those in healthy subjects.

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Authors and Affiliations

  1. Pharmacokinetics and Biopharmaceutics Department, Abbott Laboratories, D4PK, AP13A, 100 Abbott Park Road, Abbott Park, Illinois, 60064-3500, USA

    Walid M. Awni, Rene A. Braeckman & G. Richard Granneman

  2. Clinical Pharmacology Department, Abbott Laboratories, Abbott Park, Illinois, USA

    John H. Cavanaugh

  3. Chiron Corporation, Emeryville, California, USA

    Rene A. Braeckman

  4. Drug Analysis Department, Abbott Laboratories, Abbott Park, Illinois, USA

    Sou-yie (Maury) Chu

  5. Statistics Department, Abbott Laboratories, Abbott Park, Illinois, USA

    Karen J. Patterson

  6. Biotransformation Department, Abbott Laboratories, Abbott Park, Illinois, USA

    Joseph M. Machinist

Authors
  1. Walid M. Awni
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  2. John H. Cavanaugh
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  3. Rene A. Braeckman
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  4. Sou-yie (Maury) Chu
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  5. Karen J. Patterson
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  6. Joseph M. Machinist
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  7. G. Richard Granneman
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Awni, W.M., Cavanaugh, J.H., Braeckman, R.A. et al. The Effect of Mild or Moderate Hepatic Impairment (Cirrhosis) on the Pharmacokinetics of Zileuton. Clin-Pharmacokinet 29 (Suppl 2), 49–61 (1995). https://doi.org/10.2165/00003088-199500292-00008

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  • DOI: https://doi.org/10.2165/00003088-199500292-00008

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