Acute phenytoin intoxication associated with the antineoplastic agent UFT.
Antineoplastic drugs are known to affect the intestinal wall and suppress the absorption of phenytoin (PHT), resulting in a decrease in the serum PHT level. UFT (not an abbreviation) is a mixture of uracil, which enhances the activity of 5-fluorouracil (5-FU), and tegafur, a masked compound of 5-FU. The authors report three cases in which treatment of malignant brain tumors with UFT caused acute PHT intoxication. Two patients received PHT preoperatively at 150-200 and 270 mg/day, and showed serum PHT levels of less than 5 micrograms/ml. The third patient was started on 150 mg/day of PHT after surgery. Postoperatively, in addition to radiation therapy, each patient received 4 capsules of UFT (each containing 100 mg of tegafur) per day. Their serum PHT levels peaked at 48.2, 30.9, and 24.2 micrograms/ml, and all three exhibited clinical symptoms of acute PHT intoxication. The mechanism of interaction of these two drugs is obscure. Tegafur may compete with PHT in binding to metabolic enzymes in the liver and/or directly suppress PHT metabolism, leading to an increase in the serum PHT concentration. Therefore, when PHT is given in combination with a masked compound of 5-FU, the serum PHT level should be closely monitored.
Wakisaka
S
S
Department of Neurosurgery, Miyazaki Medical College.
Shimauchi
M
M
Kaji
Y
Y
Nonaka
A
A
Kinoshita
K
K
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000188:drug therapy; D003131:Combined Modality Therapy; D004347:Drug Interactions; D005260:Female; D005910:Glioma / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000506:poisoning*; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects
D005641:Tegafur; D014498:Uracil; D010672:Phenytoin