Impaired Phenytoin Bioavailability Secondary to Cisplatinum, Vinblastine, and Bleomycin

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Abstract
A 24-yr old woman experienced grand mal seizures temporally related to cisplatin, vinblastine and bleomycin (CVB) administration. A 2nd episode of seizures occurred when the patient''s phenytoin level was estimated to be in the range of 15 .mu.g/ml. Her plasma phenytoin level at the time had dropped to 2 .mu.g/ml, despite a recent dosage increase. To evaluate the cause of the subtherapeutic phenytoin levels, daily plasma phenytoin levels and 24-h urine collections were obtained during her next CVB cycle. Data revealed a mean phenytoin absorption of 32% (normal > 80%), establishing that phenytoin malabsorption occurred. The disruption of phenytoin absorption at a cellular level by CVB therapy is the proposed mechanism. Frequent monitoring of plasma phenytoin levels is recommended for patients receiving CVB.