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Acute phenytoin intoxication associated with the antineoplastic agent UFT.
S Wakisaka1, M Shimauchi, Y Kaji
1Department of Neurosurgery, Miyazaki Medical College.
Fukuoka Igaku Zasshi = Hukuoka Acta Medica
|April 1, 1990
Summary
Antineoplastic drugs can lower phenytoin (PHT) levels, but UFT treatment for brain tumors unexpectedly caused PHT intoxication in three patients. Close monitoring of PHT levels is crucial when co-administered with UFT.
Area of Science:
- Oncology
- Pharmacology
- Neuroscience
Background:
- Antineoplastic drugs can alter intestinal absorption and lower serum phenytoin (PHT) levels.
- UFT, a combination of uracil and tegafur (a 5-fluorouracil prodrug), is used for malignant brain tumors.
Observation:
- Three patients with malignant brain tumors developed acute PHT intoxication while receiving UFT and PHT concurrently.
- Pre-treatment PHT levels were therapeutic (<5 µg/ml), but increased significantly (24.2–48.2 µg/ml) after UFT administration.
Findings:
- UFT treatment led to a marked increase in serum PHT levels, causing clinical intoxication in all three patients.
- The interaction mechanism is unclear but may involve tegafur competing for or inhibiting hepatic metabolic enzymes responsible for PHT breakdown.
Implications:
- This case series highlights a critical drug interaction between UFT and PHT, necessitating careful patient monitoring.
- Clinicians should closely monitor serum PHT levels when UFT is co-administered to prevent potentially toxic accumulation.