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

Abstract: Abstract: Objective To establish a Physiologically-based pharmacokinetic (PBPK) modeling for vitamin D3 （Vd3）in adults, thereby recommending appropriate clinical dosages for individuals with vitamin D（Vd） deficiencies. Methods A comprehensive review of relevant literature and databases was conducted to gather the physicochemical properties and pharmacokinetic parameters of Vd3. Subsequently, the PK-Sim? software was utilized to construct, optimize, and predict the whole-body PBPK model of Vd3 in adults. The model's predictive performance was evaluated based on confidence intervals, goodness-of-fit, and fold error. Based on the optimized model, the effectiveness of current clinical dosing regimens was further assessed, and personalized dosage recommendations were provided. Results The goodness-of-fit, R2 of 0.961 is close to 1 and FE values for AUC0-∞ and Cmax between 0.5 and 2 indicating the established adult whole-body PBPK model has excellent predictive capabilities. Conclusion Successfully constructed the adult PBPK model for oral Vd3 supplementation, the model demonstrates good predictive performance for a single oral dose of Vd3. A single oral dose of Vd3 (7 500 μg and 15000 μg) is considered a safe and effective dosing regimen to ameliorate Vd insufficiency/deficiency in Asian adults. Before and during the treatment, regular monitoring of 25(OH)D3 levels should be conducted to achieve the optimal outcome of personalized therapy.

Key words: itamin D3, PK-Sim?, PBPK, pharmacokinetics, goodness of fit, dose prediction