ACS-SIMULATOR: A Shiny Application for Guiding Antenatal Corticosteroid Administration in Pregnant Women

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 maturity[ 1]. 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) model[ 2]. 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 framework[ 3], ACS-SIMULATOR uses a published hybrid mPBPK model[ 2] 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); AUC 0-72h 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); AUC 0-72h 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); AUC 0-72h 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); AUC 0-72h 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.