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Identification of propafenone metaboliser phenotype from plasma and urine excretion data

European Journal of Clinical Pharmacology volume 42, pages 111–114 (1992)Cite this article

Summary

The aim of the study was to validate a test based on analyses of urine to identify the propafenone metaboliser phenotype during routine chronic therapy. Twenty seven patients chronically treated with propafenone were studied. A debrisoquine test was performed in 10. Propafenone and its metabolites in plasma and urine were measured by HPLC. Propafenone, 5-hydroxypropafenone and N-depropylpropafenone concentrations in plasma were 1.09, 0.182 and 0.101 ng·ml−1, respectively. Total recovery of the administered dose in urine was 30.7%. Two patients were identified as PM, based on the result of the debrisoquine test (log D/4OHD of 1.26 and 1.36). This finding was confirmed by the propafenone metabolic ratio in urine, but the plasma data did not permit clearcut separation of the phenotypes. Propafenone/5-hydroxypropafenone in plasma was not a good predictor of metabolizer phenotype. Although the number of patients who completed all three tests was limited, it is concluded that analysis of propafenone/5-hydroxypropafenone in urine collected between two consecutive doses at steady-state is more practical than the debrisoquine test and more specific than determining the propafenone/5-hydroxypropafenone ratio in plasma, for identification of the propafenone metaboliser phenotypes.

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Affiliations

  1. Istituto di Ricerche Famacologiche Mario Negri, Milano, Italy

    R. Latini, R. Bernasconi & D. Leopaldi

  2. Ospedale di Seriate, Bergamo, Italy

    M. Belloni, P. Giani & M. Landolina

  3. Ospedale L. Sacco, Milano, Italy

    E. Cappiello

  4. Divisio de Farmacologia Clinica, Universitat Autonoma de Barcelona, Spain

    J.-M. Castel

Authors
  1. R. Latini
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  2. M. Belloni
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  3. R. Bernasconi
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  4. E. Cappiello
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  5. P. Giani
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  6. M. Landolina
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  7. D. Leopaldi
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  8. J.-M. Castel
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Latini, R., Belloni, M., Bernasconi, R. et al. Identification of propafenone metaboliser phenotype from plasma and urine excretion data. Eur J Clin Pharmacol 42, 111–114 (1992). https://doi.org/10.1007/BF00314930

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  • DOI: https://doi.org/10.1007/BF00314930

Key words

  • Propafenone
  • Debrisoquine
  • pharmacogenetics
  • phenotype analysis
  • metabolism