Impaired phenytoin bioavailability secondary to cisplatinum, vinblastine, and bleomycin

A 24-year-old woman experienced grand mal seizures temporally related to cisplatin, vinblastine, and bleomycin (CVB) administration. A second episode of seizures occurred when the patient's phenytoin level was estimated to be in the range of 15 micrograms/ml. Her plasma phenytoin level at the time had dropped to 2 microgram/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 greater than 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.