Optimal Dosing of Understudied Drugs Administered to Pregnant Individuals per Standard of Care (PregDose)

/ABSTRACT The majority of drugs prescribed to pregnant individuals lack dosing information specific to this population. Dosing is different in this population due to anatomic and physiologic changes during pregnancy that substantially affect drug exposure. A lack of appropriate dosing data in pregnant individuals is an unmet public health need that can result in therapeutic failure and maternal and fetal morbidity. Our objective for the Dosing and Safety of Understudied Drugs Administered to Pregnant Individuals per Standard of Care (PregDose) Study is to create the research infrastructure to address these dosing knowledge gaps and determine optimal dosing for commonly used drugs in pregnancy. We will accomplish this goal through an integrated approach that is centered on a prospective, multi-center, opportunistic study of understudied drugs in pregnant individuals. In AIM 1, we will enroll pregnant individuals who are on a drug(s) of interest per standard of care. Biological samples and markers of drug efficacy will be collected throughout pregnancy and in the postpartum period. Postpartum samples will also include cord blood and infant blood to better understand fetal/neonatal exposure. Using an aliquot of each sample, in AIM 2 we will establish a biorepository to aid future precision- dosing studies. In AIM 3 we will use sophisticated pharmacokinetic (PK)-pharmacodynamic (PD) modeling to determine optimal dosing. This modeling will identify key determinants of drug exposure-effect to inform a pregnancy precision dosing tool. The PIs and research team have a successful history in maternal pharmacology and possess the skills, access to patients, and research environment needed to complete these projects. Dr. Rebecaa Clifton is a biostatistician, the PI of the Maternal-Fetal Medicine Units (MFMU) Data Coordinating Center and will oversee all study efforts. Dr. Watt is a pediatrician, experienced trialist and pharmacologist, serves on the PRGLAC Implementation Working Group, and has led similar opportunistic dosing studies in children and lactating individuals. Dr. Torri Metz is a maternal fetal medicine specialist with extensive experience in obstetric drug trials. Importantly, this study will leverage the infrastructure and resources of the NICHD-funded MFMU Network and Maternal and Pediatric Precision in Therapeutics (MPRINT) Hub. Key MPRINT co-investigators have the expertise and resources to develop the assays to measure drug concentrations (Momper), support the PK-PD modeling (Quinney, Momper, Bies), and develop the model-informed precision dosing tool (Quinney, Bies). To maximize scientific exchange and accelerate research in the field, all information, data, protocols, resources, and methods developed by PregDose will be shared through the MFMU and MPRINT Hub and with the research and clinical community at large. Project Number: 1U01HD118959-01 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Rebecca Clifton (+2 co-PIs) | Institution: GEORGE WASHINGTON UNIVERSITY, WASHINGTON, DC | Award Amount: $1,669,596 | Activity Code: U01 | Study Section: Special Emphasis Panel[ZHD1 DSR-C (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1U01HD11895901