关键词: 维生素D3, PK-Sim^®, PBPK, 药代动力学, 拟合优度, 剂量预测

Abstract: AIM: To establish a physiologically-based pharmacokinetic (PBPK) model for vitamin D in adults, aiming to provide guidance for the rational clinical use of vitamin D in individuals with vitamin D deficiency. METHODS: Relevant literature and databases were reviewed to obtain the physicochemical properties and pharmacokinetic parameters of vitamin D3. The PBPK model for adult whole-body vitamin D was constructed, optimized, and predicted using PK-Sim^® software. The model's predictive performance was evaluated using confidence intervals, goodness of fit, and fold error (FE). The effectiveness of commonly used clinical dosing regimens was assessed based on the final optimized model, and personalized dosing recommendations were provided. RESULTS: The established adult whole-body PBPK model for vitamin D had a goodness of fit R² of 0.961, approaching 1, and the FE values for AUC_0-∞ and C_max were both within the range of 0.5 and 2, indicating that the constructed PBPK model possesses good data predictive capability. CONCLUSION: A successful PBPK model for oral vitamin D3 in adults has been established, showing good predictive performance for single oral doses of vitamin D3. Single oral doses of vitamin D3 (7 500 μg and 15 000 μg) are safe and effective dosing regimens for improving vitamin D insufficiency or deficiency in Asian adults. Regular monitoring of vitamin D levels before and during treatment is recommended to achieve the optimal outcomes of personalized therapy.

Key words: vitamin D3, PK-Sim^®, PBPK, pharmacokinetics, goodness of fit, dose prediction