Physiological-based Pharmacokinetics Approach to Medication Exposure During Pregnancy and Breastfeeding (PBPK)

University of Pittsburgh

Status: Enrolling

Conditions: Epilepsy; Pregnancy Related

Treatments: Drug: Levetiracetam; Drug: Oxcarbazepine; Drug: Lamotrigine

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT05450978

R01HD105305 (U.S. NIH Grant/Contract)

STUDY21090138

Details and patient eligibility

About

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.

Full description

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:

1. Adjust doses in practice without obtaining frequent visits to the lab for therapeutic drug monitoring.
2. 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:

1. Drug concentrations obtained in preconception and early pregnancy predict clearance changes throughout the remainder of pregnancy for individual pregnant women with epilepsy.
2. 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).

Enrollment: 60 estimated patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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)

Exclusion criteria

• 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).

Trial design

60 participants in 3 patient groups

Lamotrigine (LTG)

Description:

Participants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with lamotrigine (LTG)

Treatment:

Drug: Lamotrigine

Levetiracetam (LEV)

Description:

Participants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with Levetiracetam (LEV)

Treatment:

Drug: Levetiracetam

Oxcarbazepine (OXC)

Description:

Participants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with with Oxcarbazepine (OXC)

Treatment:

Drug: Oxcarbazepine