PHARMACOKINETICS AND SAFETY OF INTRAVENOUS TOPIRAMATE IN ADULT PATIENTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项首次在成人中服用托吡酯(TPM)的人体研究的目的是提供必要的信息，进一步将TPM作为一种孤儿产品，用于治疗新生儿缺氧缺血性脑病(HIE)的新生儿癫痫发作，HIE是一种罕见的医学疾病。在对新生儿进行研究药物之前，FDA要求首先在成年人身上进行研究。我们正在开展一种新型静脉注射TPM制剂在服用口服TPM的成人患者中的药代动力学和安全性研究。小剂量(25毫克)的稳定标记(非放射性)TPM与患者通常早晨服用的剂量同时给予。对输液部位、全身和神经不良反应进行评估。可以测量口服和静脉注射TPM剂量的血浆TPM浓度，并且可以在不中断患者维持方案的情况下确定完整的药代动力学曲线。这项先导性研究的结果将为后续研究的设计提供参考，包括旨在确定静脉注射TPM对新生儿神经保护和癫痫控制的有效性和安全性的对照临床试验。

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.