PHARMACOKINETICS AND SAFETY OF INTRAVENOUS TOPIRAMATE IN ADULT PATIENTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The aim of this first-in-humans study in adults taking oral topiramate (TPM) is to provide information essential to the further development of TPM as an orphan product for the treatment of neonatal seizures in newborns with hypoxic-ischemic encephalopathy (HIE), a rare medical disorder. Prior to studies of investigational drugs in newborns, the FDA requires that studies first be done in adults. We are carrying out a pharmacokinetic and safety study of a novel, intravenous TPM formulation in adult patients taking oral TPM. A small (25 mg) dose of a stable-labeled (non-radioactive) TPM is given at the same time as the patient takes his or her usual morning dose. Infusion site, systemic, and neurological adverse effects are assessed. Plasma TPM concentrations from both oral and IV TPM doses are measured and a full pharmacokinetic profile can be determine without interrupting patients' maintenance regimen. Results from this pilot study will inform the design of subsequent studies, including controlled clinical trials intended to determine the efficacy and safety of IV TPM for neuroprotection and seizure control in neonates.