Felbamate in term infants with hypoxic ischemic encephalopathy

Abstract

Felbamate, a non-selective anticonvulsant thought to act via blocking the N-methyl-D-aspartate receptor, has been shown in animal studies not only to block seizures, but also to be neuroprotective. Excessive discharge of the excitatory pathways, involving primarily the glutamate receptor system, is important in the cascade of neuronal injury in hypoxic ischemic encephalopathy (HIE). Because of renewed interest in adjunctive therapy in addition to hypothermia to minimize hypoxic ischemic injury in neonates, we report the absorption and time to peak level of felbamate preliminary to testing its neuroprotective effects in this population. A single dose of either 45 mg/kg or 200 mg/kg of felbamate was given via nasogastric tube to four infants with severe HIE. We measured serum felbamate levels at 2, 4, 8, 12 and 24 hours after administration of the drug. Oral absorption of felbamate is slow. Peak levels of 40–64 μg/mL were achieved at 12 to 24 hours in the two infants who received 200 mg/kg dose. In conclusion, oral felbamate is unsuitable for infants with HIE as oral doses are unlikely to reach adequate neuroprotective levels in a timely fashion.

Keywords

Neuroprotection - HIE - newborn - felbamate