PBPK: Physiological-based Pharmacokinetics Approach to Medication Exposure During Pregnancy and Breastfeeding
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
Detailed 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:
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Adjust doses in practice without obtaining frequent visits to the lab for therapeutic drug monitoring.
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Predict exposure of LTG and LEV in mothers and their infants in order to maintain the individualized target concentrations, thus protecting mothers from seizure worsening and minimizing fetal toxicity.
Hypotheses:
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Drug concentrations obtained in preconception and early pregnancy predict clearance changes throughout the remainder of pregnancy for individual pregnant women with epilepsy (WWE).
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Lamotrigine (LTG) Participants will include women with epilepsy planning pregnancy within the next 6 months and treated with lamotrigine (LTG) |
Drug: Lamotrigine
Anti-seizure concentrations
Other Names:
|
| Levetiracetam (LEV) Participants will include women with epilepsy planning pregnancy within the next 6 months and treated with Levetiracetam (LEV) |
Drug: Levetiracetam
Anti-seizure concentrations
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Anti-Seizure Medication (ASM) Clearance [Through study completion, an average of 18 months.]
ASM Clearance will be calculated from measurements of lamotrigine 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.
Secondary Outcome Measures
- Seizure Frequency [Through study completion, an average of 18 months.]
Participants will keep a daily seizure diary throughout their participation in the study. The diary will be reviewed at each study visit.
- Anti-seizure Medication (ASM) Side Effects [Through study completion, an average of 18 months]
An ASM Side Effect Questionnaire will be administered and a neurologic examination will be performed at each study visit.
- Placental passage of Anti-Seizure Medications (ASM) [Through study completion, an average of 18 months]
Maternal blood will be drawn and umbilical cord blood will be collected, for measurements of ASM concentrations for lamotrigine and levetiracetam.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Women planning pregnancy within the next 6 months.
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Women currently being treated with lamotrigine (LTG) or levetiracetam (LEV) for a diagnosis of epilepsy
Exclusion Criteria:
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History of psychogenic non-epileptic spells
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History of other major medical illnesses including renal or hepatic disease, progressive cerebral disease,
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Inability to maintain a seizure and medication daily diary
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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 or levetiracetam).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Kaufmann Medical Building | Pittsburgh | Pennsylvania | United States | 15213 |
Sponsors and Collaborators
- Page B. Pennell, MD
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
- Principal Investigator: Page B Pennell, MD, The University of Pittsburgh
Study Documents (Full-Text)
More Information
Publications
- Birnbaum AK, Meador KJ, Karanam A, Brown C, May RC, Gerard EE, Gedzelman ER, Penovich PE, Kalayjian LA, Cavitt J, Pack AM, Miller JW, Stowe ZN, Pennell PB; MONEAD Investigator Group. Antiepileptic Drug Exposure in Infants of Breastfeeding Mothers With Epilepsy. JAMA Neurol. 2020 Apr 1;77(4):441-450. doi: 10.1001/jamaneurol.2019.4443.
- Pennell PB, French JA, May RC, Gerard E, Kalayjian L, Penovich P, Gedzelman E, Cavitt J, Hwang S, Pack AM, Sam M, Miller JW, Wilson SH, Brown C, Birnbaum AK, Meador KJ; MONEAD Study Group. Changes in Seizure Frequency and Antiepileptic Therapy during Pregnancy. N Engl J Med. 2020 Dec 24;383(26):2547-2556. doi: 10.1056/NEJMoa2008663.
- Pennell PB, Karanam A, Meador KJ, Gerard E, Kalayjian L, Penovich P, Matthews A, McElrath TM, Birnbaum AK; MONEAD Study Group. Antiseizure Medication Concentrations During Pregnancy: Results From the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) Study. JAMA Neurol. 2022 Apr 1;79(4):370-379. doi: 10.1001/jamaneurol.2021.5487.
- STUDY21090138
- R01HD105305