Plasma Protein Binding and Blood-to-Plasma Ratios of Atractylodin and -Eudesmol, the Bioactive Compounds from Atractylodes lancea (Thunb.) D.C.

Cholangiocarcinoma remains a problem in several tropical and subtropical parts of the world, especially in Southeast Asia. The study determined plasma protein binding and blood-to-plasma ratio (B:P) of atractylodin (AT) and β-eudesmol (BE), the two active constituents of Atractylodes lancea (Thunb.) D.C., which is currently under development as an alternative treatment for cholangiocarcinoma. Plasma protein binding studies were performed using the ultracentrifugation method. Plasma samples (n=10) were spiked with AT or BE (2.5, 5, and 10 µg/mL) and incubated at 37 °C for 1 h. Blood to plasma (B:P) ratios of both compounds (0.5 mg/ml) were determined in human plasma produced from the spiked whole blood and the spiked plasma (n=10 each) and incubated at 37 °C for 10 min and 1 hour, respectively. Concentrations of AT and BE were determined using HPLC-UV. Plasma protein binding (%PPB) of AT and BE were relatively high (>90%), with low unbound fractions (fu < 0.05). The AT and BE concentrations in plasma and red blood cells (RBCs) were comparable, with the KRBC/Plasma (B:P) ratio of about 1. The high partitioning in blood circulation and high plasma protein binding of AT and BE may limit the extent of their distribution and delivery to the target tissues (bile ducts). Either plasma or whole blood can be used as the matrix of choice for pharmacokinetic studies. The information obtained would provide essential input parameters in the pharmacokinetic models to predict optimal dose regimens of AL in clinical studies.