Predicting Pharmacokinetics of Active Constituents in Spatholobi caulis by Using Physiologically Based Pharmacokinetic Models

Background/Objectives: Spatholobi Caulis (SPC) is a medicinal plant that mainly grows in China and Southeast Asian countries and commonly used in clinics; the pharmacokinetic characteristics in humans need to be determined. This study was to establish the physiologically based pharmacokinetic (PBPK) models of multiple active constituents from SPC in rats, and predict the pharmacokinetic properties of rats with different dosages and extrapolated to humans. Methods: The parameters were collected based on our previous study and by prediction using ADMET Predictor software predict. The PBPK models for 3′-methoxydadizein (1), 8-O-methylretusin (2), daidzin (3), and isolariciresinol (4) administered orally to rats were established using GastroPlus software. These models were employed to simulate the pharmacokinetic properties in rats across various dosages, and subsequently extrapolated to humans. The calculated parameters including Cmax, Tmax, and AUC were compared with observed values. The accuracy of the PBPK models was assessed using fold-error (FE) values. Result: The FE values ranged from 1.03 to 1.52, meeting the PBPK model regulations where FE should be less than 2. The sensitivity analysis focusing on the absorption amount and AUC0→t of these four constituents in humans was also conducted. These results confirm the successful establishment of PBPK models of these four constituents from SPC in this study, and these models were applicable to predict pharmacokinetics across various doses and extrapolate across species. Conclusions: The PBPK models of four constituents can be used to predict the pharmacokinetic characteristics in humans after oral administration of SPC and provide useful data for safe and rational medication in clinical practice.