Clinical Pharmacokinetics

, Volume 25, Issue 2, pp 136–144 | Cite as

The Relationship between Phenazone (Antipyrine) Metabolite Formation and Theophylline Metabolism in Healthy and Frail Elderly Women

  • Kees Groen
  • Michael A. Horan
  • Nicholas A. Roberts
  • Ravi S. Gulati
  • Branislava Miljkovic
  • Evelien J. Jansen
  • Vigi Paramsothy
  • Douwe D. Breimer
  • Cornells F. A. van Bezooijen
Original Research Article

Summary

The influence of aging on the metabolism of phenazone (antipyrine), and the relationship between the formation of 3 phenazone metabolites and the metabolic clearance of theophylline in healthy and frail elderly women, were examined. Whereas the elimination half-life did not change, clearance of phenazone decreased by about 50% with age in healthy women receiving phenazone without theophylline. However, the summation of the urinary recovery of phenazone and the measured metabolites, expressed as percentage of the phenazone dose, was lower in the healthy elderly (37 ± 9% vs 74 ± 15%).

In both healthy and frail females the clearance of formation of 4-hydroxy-phenazone and the metabolic clearance of theophylline correlated strongly (r = 0.93 and 0.90, respectively). In nonhealthy elderly females, strong correlations were also observed between the other metabolic pathways of phenazone and the metabolic clearance of theophylline. Coadministration of theophylline in the elderly increased the percentage of the phenazone dose excreted as the measured metabolites. A considerably higher interindividual variability in the disposition of phenazone and theophylline was observed in the frail elderly women. This high degree of variability in drug metabolism may be one of the explanations for the problems often occurring after drug prescription in the elderly.

Keywords

Theophylline Oral Contraceptive Antipyrine Metabolic Clearance Phenazone 

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Copyright information

© Adis International Limited 1993

Authors and Affiliations

  • Kees Groen
    • 1
    • 3
  • Michael A. Horan
    • 2
  • Nicholas A. Roberts
    • 2
  • Ravi S. Gulati
    • 2
  • Branislava Miljkovic
    • 1
  • Evelien J. Jansen
    • 1
  • Vigi Paramsothy
    • 2
  • Douwe D. Breimer
    • 3
  • Cornells F. A. van Bezooijen
    • 1
  1. 1.The Netherlands Organisation for Applied Scientific Research (TNO)Institute of Ageing and Vascular ResearchLeidenThe Netherlands
  2. 2.Department of Geriatric MedicineUniversity of ManchesterManchesterEngland
  3. 3.Centre for Bio-Pharmaceutical Sciences, Division of PharmacologyUniversity of LeidenLeidenThe Netherlands

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