(T-014) ACS-SIMULATOR: A Shiny Application for Guiding Antenatal Corticosteroid Administration in Pregnant Women

Keerthana Rajkumar – Department of Pharmaceutical Sciences – University at Buffalo; Wojciech Krzyzanski – Department of Pharmaceutical Sciences – University at Buffalo

Objectives: Respiratory distress syndrome (RDS) is a leading cause of neonatal morbidity in preterm births. Antenatal corticosteroids (ACS) are standard therapy to promote fetal lung maturity¹. However, prolonged or excessive exposure may be harmful. This project developed ACS-SIMULATOR, a Shiny app simulating maternal-fetal pharmacokinetics using a minimal PBPK (mPBPK) model². The tool enables real-time adjustment of dosing parameters and visualization of maternal and fetal drug exposure to support regimen selection.

Methods: Built in R (v4.4.0) with the Shiny framework³, ACS-SIMULATOR uses a published hybrid mPBPK model² incorporating maternal-fetal plasma and tissue compartments connected via the placenta. Simulations run via rxode2 (v2.1.3)⁴ to solve ODEs efficiently. Users can select a drug from Dexamethasone phosphate(DEX-P), Betamethasone phosphate (BET-P), Betamethasone phosphate-acetate (BET-PA), then define route, dose, interval, number of doses, and duration. The app outputs concentration-time profiles via ggplot2 and computes PK parameters (Cmax, Ctrough, Tmax, AUC) using a custom function (nca_calculator()) that handles single/multiple dosing and resolves Tmax plateaus. Outputs include plots, tables, and downloadable data.

Results: ACS-SIMULATOR was used to simulate two case studies that reflect real-world ACS dosing recommendations.
Case Study 1: WHO-Recommended Regimens
DEX-P 6 mg i.m. q12h ×4 produced Cmax 50.95 ng/mL (maternal), 14.28 ng/mL (fetal); Ctrough 5.21 ng/mL (maternal), 1.62 ng/mL (fetal); AUC₀₋₇₂h 882 ng·h/mL (maternal), 266.48 ng·h/mL (fetal) while
BET-P 12 mg i.m. q24h ×2 produced Cmax 92.3 ng/mL (maternal), 25.36 ng/mL (fetal); Ctrough 17.59 ng/mL (maternal), 4.97 ng/mL (fetal); AUC₀₋₇₂h 2462.27 ng·h/mL (maternal), 684.20 ng·h/mL (fetal).
Case Study 2: ACTION-III Trial Simulation
Low dose BET-P vs standard DEX-P
BET-P 2 mg i.m. q12h ×4: Cmax 21.16 ng/mL (maternal), 5.95 ng/mL (fetal); Ctrough 10.06 ng/mL (maternal), 2.86 ng/mL (fetal); AUC₀₋₇₂h 798.27 ng·h/mL (maternal), 221.72 ng·h/mL (fetal).
DEX-P 6 mg i.m. q12h ×4: Cmax 50.95 ng/mL (maternal), 14.28 ng/mL (fetal); Ctrough 5.21 ng/mL (maternal), 1.62 ng/mL (fetal); AUC₀₋₇₂h 882 ng·h/mL (maternal), 266.48 ng·h/mL (fetal).

Conclusions: ACS-SIMULATOR translates complex pharmacometric models into a user-friendly clinical tool, enabling interactive, data-driven decisions. It promotes individualized therapy and optimized ACS dosing in pregnancy, thus bridging model-based science with bedside care.

Citations: [1] Committee Opinion No. 677. ACOG Committee Opinion: Antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol. 2016;128:e187–e194.
[2] Krzyzanski W, Milad MA, Jobe AH, Jusko WJ. Minimal physiologically-based hybrid model of pharmacokinetics in pregnant women: Application to antenatal corticosteroids. CPT Pharmacometrics Syst Pharmacol. 2023;12(5):668–680. doi:10.1002/psp4.12899
[3] Chang W, Cheng J, Allaire JJ, et al. shiny: Web Application Framework for R (Version 1.10.0). CRAN. https://CRAN.R-project.org/package=shiny
[4] Wang W, Matott RS, Holford N. rxode2: Fast ordinary differential equation solvers for pharmacometrics. https://nlmixr2.github.io/rxode2/

Keywords: shiny, mPBPK model, antenatal corticosteroids