(125) Development of Physiologically Based Pharmacokinetics Model of Aspirin in Pregnancy

Thursday, January 30, 2025

10:30 AM – 12:30 PM

Submitting Author and Presenting Author(s)

Ana Collins-Smith, BS, MD (she/her/hers)

Fellow Physician
University of Texas Medical Branch
Galveston, Texas, United States

Coauthor(s)

Ananth Kammala, Pharm D

Assistant professor
University of Texas Medical Branch
Galveston, Texas, United States
Ramkumar Menon, PhD

Director
University of Texas Medical Branch
Galveston, Texas, United States

Objective: Aspirin is one of the most commonly used over-the-counter medications in pregnancy, particularly for the prevention of hypertensive disorders. However, there are limited studies on aspirin's pharmacokinetics (PK) in pregnant women. This study aimed to develop a pregnancy-specific physiologically based pharmacokinetic (PBPK) model for aspirin that could be individualized to patient specific parameters; illustrating differences in aspirin pharmacokinetics across the different trimesters of pregnancy.

Study Design: A PBPK model was developed using GastroPlus™ (a mechanistically based simulation software) for nonpregnant and pregnant subjects, including each trimester of pregnancy. The nonpregnant PBPK model was first established and validated against existing data from healthy adult volunteers. Once validated, the model was adapted for pregnant subjects and verified using observed pharmacokinetic profiles.

Results: The simulated PK parameters of aspirin in pregnant and nonpregnant women closely matched the clinical observations reported in the literature, with fold errors ≤1.04 (less than 1.5 is considered an acceptable simulation model). The predicted systemic exposure (AUC₀₋₂₄h) to aspirin decreased throughout gestation, showing a reduction of approximately 20% at 10 weeks and 30% at 40 weeks of gestation. An increase in clearance of approximately 3% was observed as gestation progressed.

Conclusion: A validated PBPK model using GastroPlus™ was developed to describe the pharmacokinetics and pharmacodynamics of aspirin in both pregnant and nonpregnant healthy adults. The model predicted a modest decrease of 10% in systemic exposure in pregnant women and a 20% increase in fetal exposure to aspirin as pregnancy progresses. The increasing fetal exposure with advancing gestational age may pose potential safety risks to the fetus.