Delayed onset epilepsy after intracranial surgery has been observed in our neurosurgery ward. We performed a clinical pharmacy service using therapeutic drug monitoring (TDM) during treatment with zonisamide (ZNS) for a 46-year-old woman who had a high risk of postoperative epilepsy. We administered medication of ZNS 200 mg/day a week before surgery and assessed its prophylactic efficacy against postoperative late epilepsy. On the fourth day of therapy, the plasma concentrations of ZNS measured using HPLC just before and 2 hours after drug administration were 9.3 and 12.3μg/ml, respectively. On the seventh day of therapy, the plasma concentrations just before and immediately after surgery were 10.6 and 7.0μg/ml, respectively. On the second and third days after surgery, transient sensory seizures developed and the plasma concentrations were 9.0 and 11.0μg/ml, respectively. Subsequently the dosage of ZNS was increased to 300 mg/day. On the sixth and tenth days after surgery, similar seizures again developed and the plasma concentrations at that time were 15.2 and 15.6μg/ml, respectively. Therefore, the dosage of ZNS was further increased to 400 mg/day. On the twenty-fourth day after surgery, the plasma concentration was 21.0μg/m1 and no further seizures were subsequently noted. The patient was discharged one month after the operation with no complications.
Prophylactic anticonvulsant therapy after intracranial surgery remains controversial, but our observations suggested that ZNS may thus be useful for preventing postoperative late epilepsy. TDM was thus found to provide important pharmacokinetic information to effectively control the medication dosage in patients at high risk for developing postoperative epilepsy.