Abstracts

RATIONALE: Most antiseizure medications are available only as orally administered formulations. In an epilepsy patient who is maintained on a stable regimen with one antiseizure drug, the abrupt interruption of oral therapy due to a medical emergency can cause breakthrough seizures which complicates patient care. We report on the rectal administration of topiramate (TPM) in a patient with epilepsy who was unable to continue oral therapy during hospitalization.
METHODS: A 46-year-old mentally retarded male with complex partial seizures and severe obsessive compulsive disorder was admitted to the hospital with a small bowel perforation. At admission, his seizures were controlled with a vagal nerve stimulator, phenobarbital (PB, 150 mg/day), and TPM (200 mg/day). Postoperatively, the patient had an ileus; PB was continued with I.V. administration but the patient could not receive oral TPM. When the patient was NPO for more than 24 hrs, the likelihood of seizures became a concern. The patient[scquote]s history of severe behavioral problems precluded an increase in PB dose, necessitating rectal administration of TPM. Assuming that the bioavailability of rectally administered TPM would be less than orally administered drug, the TPM dose was increased to 300 mg/day (100 mg in AM; 200 mg in PM). Tablets were crushed, resuspended in 0.9% saline, and injected into the rectal vault every 12 hours. Blood levels were measured during and after hospitalization.
RESULTS: The patient remained seizure-free during rectal administration of TPM despite development of adult respiratory distress syndrome. Prior to hospitalization, the TPM blood level was 4.5 [mu]g/ml with 200 mg qd oral TPM, which dropped to [mu]g/ml ~48 hrs after TPM was discontinued. After three rectal doses of TPM (200 mg, 100 mg, and 200 mg respectively) over 36 hours, TPM trough levels were 1.7 [mu]g/ml. PB levels remained constant with I.V. administration. After hospitalization, the patient remained on 300 mg/day TPM orally; TPM serum concentrations at three subsequent office visits were 4.8 [mu]g/ml, 4.9 [mu]g/ml, and 4.3 [mu]g/ml over 4 months.
CONCLUSIONS: Although TPM blood levels during rectal administration were lower than during oral administration, the TPM level was sufficient to keep the patient seizure-free during the period in which oral therapy was interrupted. These observations suggest that TPM doses administered rectally as a suspension is less bioavailable than oral tablets and that TPM doses should be increased for rectal administration. Pharmacokinetic studies are needed to determine the degree to which TPM doses should be increased for rectal administration in order to maintain blood levels achieved orally.