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Phenytoin auto-induction? Case reports.

R Miller1, P L Bill, J Du Toit

  • 1Department of Pharmacology, University of Durban-Westville.

South African Medical Journal = Suid-Afrikaanse Tydskrif Vir Geneeskunde
|April 1, 1989
PubMed
Summary
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Auto-induction of phenytoin metabolism, often dismissed as minor, was observed to increase significantly in two patients. This finding suggests enzyme induction may contribute to therapeutic failure, impacting treatment choices.

Area of Science:

  • Pharmacology
  • Clinical Pharmacy
  • Drug Metabolism

Background:

  • Phenytoin is an anticonvulsant medication with a narrow therapeutic index.
  • Its metabolism is primarily hepatic, involving cytochrome P450 enzymes.
  • Auto-induction, the process by which a drug increases its own metabolism, is generally considered minimal for phenytoin.

Observation:

  • Two distinct cases are presented where continuous phenytoin use led to a notable increase in its elimination rate.
  • Patient 1 demonstrated an increase in maximal elimination capacity (Vmax) from 511 mg/day to 613 mg/day over five months.
  • Patient 2 exhibited an increase in Vmax from 512 mg/day to 570 mg/day over one year, with no compliance issues.

Findings:

  • The observed increases in phenytoin elimination capacity suggest significant auto-induction may occur.

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  • These changes were documented in patients with consistent medication adherence.
  • The data challenges the prevailing view of insignificant auto-induction for phenytoin.

    • Implications:

    • Recognizing phenytoin auto-induction is crucial for identifying causes of therapeutic failure.
    • This understanding can help clinicians avoid unnecessary diagnostic tests.
    • Identifying enzyme induction can guide adjustments in phenytoin dosage or alternative therapeutic strategies.