European Journal of Clinical Pharmacology

, Volume 66, Issue 8, pp 791–795 | Cite as

Fluconazole-induced intoxication with phenytoin in a patient with ultra-high activity of CYP2C9

  • Anders Helldén
  • Ulf Bergman
  • Karin Engström Hellgren
  • Michèle Masquelier
  • Ingela Nilsson Remahl
  • Ingegerd Odar-Cederlöf
  • Margareta Ramsjö
  • Leif Bertilsson
Pharmacogenetics
First Online:
Received:
Accepted:

Abstract

Purpose

The cytochrome P450 enzyme CYP2C9 metabolizes several important drugs, such as warfarin and oral antidiabetic drugs. The enzyme is polymorphic, and all known alleles, for example, CYP2C9*2 and*3, give decreased activity. Ultra-high activity of the enzyme has not yet been reported.

Methods

We present a patient with Behçet’s disease who required treatment with high doses of phenytoin. When fluconazole, a potent inhibitor of CYP2C9, was added to the treatment regimen, the patient developed ataxia, tremor, fatigue, slurred speech and somnolence, indicating phenytoin intoxication. On suspicion of ultra-high activity of CYP2C9, a phenotyping test for CYP2C9 with losartan was performed.

Results

The patient was shown to have a higher activity of CYP2C9 than any of the 190 healthy Swedish Caucasians used as controls.

Conclusions

Our finding of an ultrarapid metabolism of losartan and phenytoin may apply to other CYP2C9 substrates, where inhibition of CYP2C9 may cause severe adverse drug reactions.

Keywords

Behçet’s disease Losartan Ultrarapid metabolizer 
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Notes

Acknowledgments

This work was supported by grants from the Swedish Research Council, Medicine (3902) and from Karolinska Institutet.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Anders Helldén
    • 1
  • Ulf Bergman
    • 1
  • Karin Engström Hellgren
    • 2
  • Michèle Masquelier
    • 1
  • Ingela Nilsson Remahl
    • 3
  • Ingegerd Odar-Cederlöf
    • 1
  • Margareta Ramsjö
    • 1
  • Leif Bertilsson
    • 1
  1. 1.Department of Laboratory Medicine, Karolinska Institutet, Division of Clinical PharmacologyKarolinska University HospitalHuddingeSweden
  2. 2.Karolinska Institutet, Department of RheumatologyKarolinska University HospitalHuddingeSweden
  3. 3.Karolinska Institutet, Department of NeurologyKarolinska University HospitalHuddingeSweden

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