Physiological-based Pharmacokinetics Approach to Determine the Extent of Drug Exposure of Antiseizure Medications During Pregnancy and Breastfeeding
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Anti-Seizure Medication (ASM) Clearance
研究概览
简要总结
This project focuses on anti-seizure medication (ASM) clearance and physiological factors determining blood concentrations in pregnant adult women with epilepsy and amounts of exposure to their unborn children and nursing infants.
详细描述
The goal of this study is to develop modeling of pharmacokinetic changes for Antiseizure medications (ASMs), lamotrigine (LTG), and levetiracetam (LEV) during pregnancy and postpartum that can be used to:
- Adjust doses in practice without obtaining frequent visits to the lab for therapeutic drug monitoring.
- Predict exposure of ASMs in mothers and their infants in order to maintain the individualized target concentrations, thus protecting mothers from seizure worsening and minimizing fetal toxicity.
Hypotheses:
- Drug concentrations obtained in preconception and early pregnancy predict clearance changes throughout the remainder of pregnancy for individual pregnant women with epilepsy.
- Validated model allows the prediction of drug concentration changes at all stages throughout and after pregnancy, which will more accurately predict increased seizures and medication side effects.
Additionally, pilot data will be obtained for oxcarbazepine (OXC) in a small number of participants and contribute to data for ASMs that undergo glucuronidation (LTG).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Woman with epilepsy between the ages of 18-45 planning pregnancy or in the early first trimester of pregnancy.
- •Women with epilepsy ability to maintain a daily medical diary
- •Women with epilepsy ability to answer side effect questionnaires
- •Women with epilepsy currently being treated with lamotrigine (LTG) or levetiracetam (LEV) or oxcarbazepine (OXC)
排除标准
- •Women with epilepsy having history of functional seizures.
- •Women with epilepsy history of other major medical illnesses including renal or hepatic disease, progressive cerebral disease,
- •Women with epilepsy who have inability to maintain a seizure and medication daily diary
- •Women with epilepsy with present or recent history of drug or alcohol abuse, or the use of any concomitant medications that interact with the ASM they are taking (lamotrigine, levetiracetam, oxcarbazepine).
研究组 & 干预措施
Oxcarbazepine (OXC)
Participants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with with Oxcarbazepine (OXC)
干预措施: Oxcarbazepine (Drug)
Lamotrigine (LTG)
Participants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with lamotrigine (LTG)
干预措施: Lamotrigine (Drug)
Levetiracetam (LEV)
Participants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with Levetiracetam (LEV)
干预措施: Levetiracetam (Drug)
结局指标
主要结局
Anti-Seizure Medication (ASM) Clearance
时间窗: Through study completion, an average of 18 months.
ASM Clearance will be calculated from measurements of lamotrigine, oxcarbazepine, and levetiracetam blood concentrations, serum creatinine and 24-hour urine collection (for levetiracetam), glucuronidated metabolite (for lamotrigine), steroid hormones, medication formulation and doses, time since recent doses, and participant weight.
次要结局
- Seizure Frequency(Through study completion, an average of 18 months.)
- Anti-seizure Medication (ASM) Side Effects(Through study completion, an average of 18 months)
- Placental passage of Anti-Seizure Medications (ASM)(Through study completion, an average of 18 months)
研究者
Page B. Pennell, MD
Professor
University of Pittsburgh