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Principal Investigator: ANGELA K BIRNBAUM
Organization: UNIVERSITY OF MINNESOTA
Fiscal Year: 2024
Award: $539,430
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
ABSTRACT
Antiseizure medications are one of the most commonly prescribed teratogens. In pregnant women with
epilepsy, continuation of antiseizure medications and dose increases are often necessary to prevent
seizure worsening, but need to be balanced against the fetal risks of in utero exposure, such as congenital
malformations and adverse neurodevelopmental outcomes. Additionally, breastfeeding introduces another
route of drug exposure to the infant and can affect child development. Although measurement of drug
concentration in plasma is thought to reflect drug concentrations at the site of action in the mother, it is more
difficult to translate the overall exposure to the fetus or determine the full extent of the exposure to the child
through breastfeeding. Physiological-based pharmacokinetic (PBPK) methods will be used to advance a
precision medicine approach to characterize drug concentration-time profiles at the tissue level allowing
evaluation of target doses needed to achieve optimal drug exposure in women with epilepsy, taking into
account drug exposure to the fetus during pregnancy and to the breastfeeding infant. Information from both
basic science and clinical studies will be used to develop, evaluate, and validate PBPK models. This grant will
use previously collected data and new measures from existing samples in the clinical study MONEAD, animal
data, in vitro studies, and a new external validation cohort with sampling at critical timepoints (not previously
obtained) to determine the mechanistic basis of alterations in antiseizure medication concentrations during
pregnancy and lactation. These data can then be combined with outcome data in other clinical studies to
expand our knowledge of drug response and safety in women and children during two very vulnerable times,
pregnancy and lactation.
Terms: <0-11 years old><1st trimester><ASD><Affect><Animal Model><Animal Models and Related Studies><Animals><Anti-epileptic><Anticonvulsant Agent><Anticonvulsant Drugs><Anticonvulsants><Anticonvulsive Agents><Anticonvulsive Drugs><Autism><Autistic Disorder><Basic Research><Basic Science><Birth Defects><Blood Plasma><Blood flow><Body Tissues><Breast Feeding><Breast Milk><Breast fed><Breast fed infant><Breastfed><Breastfed infant><Breastfeeding><Breastmilk><Child><Child Development><Child Youth><Children (0-21)><Clinical><Clinical Data><Clinical Research><Clinical Study><Cognitive><Cohort Studies><Conceptions><Concurrent Studies><Congenital Abnormality><Congenital Anatomical Abnormality><Congenital Defects><Congenital Deformity><Congenital Malformation><Data><Data Set><Development><Dose><Drug Exposure><Drug Kinetics><Drug Monitoring><Drugs><Early Infantile Autism><Early Placental Phase><Enzyme Gene><Enzymes><Epilepsy><Epileptic Seizures><Epileptics><Evaluation><Exposure to><Fetal Tissues><Fetus><First Pregnancy Trimester><First Trimester><Gestation><Glucuronic Transferase><Glucuronosyltransferase><Glucuronyltransferase><Goals><Grant><Human Milk><Human Mother's Milk><In Vitro><Individual><Infant><Infant and Child Development><Infantile Autism><Kanner's Syndrome><Kidney><Kidney Urinary System><Knowledge><Lactation><Lamictal><Lamiktal><Late pregnancy><Levetiracetam><Mammary Gland Milk><Measurement><Measures><Medication><Methods><Modeling><Mother's Milk><Mothers><Organ><Outcome><Partition Coefficient><Pharmaceutical Preparations><Pharmacokinetics><Physiologic><Physiological><Plasma><Plasma Serum><Population><Postpartum Period><Pregnancy><Pregnant Women><Renal clearance function><Reticuloendothelial System, Serum, Plasma><Risk><Risk Assessment><Route><Safety><Sampling><Seizure Disorder><Seizures><Site><Teratogenic><Teratogenicity><Teratogens><Testing><Therapeutic><Time><Tissues><Toxic effect><Toxicities><Translating><UDP Glucuronosyltransferase><UDP Glucuronyl Transferase><Up-Regulation><Upregulation><Validation><Visit><Woman><after pregnancy><animal data><anti-epileptic agents><anti-epileptic drugs><autism spectral disorder><autism spectrum disorder><autistic spectrum disorder><breast feeding infant><breastfeeding infant><clinical care><cohort><computer based prediction><developmental><drug clearance><drug exposure in utero><drug/agent><early pregnancy><epilepsia><epileptogenic><expectant mother><expecting mother><exposed in utero><fetal><fetal exposure><fetus tissue><hepatic metabolism><in uteri drug exposure><in utero exposure><intra-uterine environmental exposure><intrauterine environmental exposure><kids><lactating><lactational><lamotrigine><liver metabolism><maternal milk><model of animal><neurodevelopment effect><neurodevelopmental effect><pharmacokinetic model><post pregnancy><post-partum><precision medicine><precision-based medicine><predictive modeling><pregnant><pregnant mothers><prenatal exposure><prenatally exposed><prevent><preventing><prospective><renal><renal clearance><response><seizure drug><seizure medication><side effect><simulation><study population><tool><validations><youngster>