Ther Drug Monit. 2000 Apr; 22(2): 155-9.

Interactions between drugs and Asian medicine: displacement of digitoxin from protein binding site by bufalin, the constituent of Chinese medicines Chan Su and Lu-Shen-Wan.

Datta P, Dasgupta A.

Bayer Diagnostics, E. Walpole, MA, USA.

Asian medicines are widely used as alternative medicine. However, interactions between drugs and Asian medicines have been poorly studied. Chan Su and Lu-Shen-Wan are Asian medicines that contain the cardiaoactive compound bufalin. Bufalin is structurally similar to digitoxin and is also strongly bound to serum albumin. The authors studied possible displacement of digitoxin from the protein binding site by bufalin. The authors prepared three serum pools from patients taking digitoxin and supplemented aliquots of each serum pool with no bufalin (control) and 25 ng/mL, 50 ng/mL, 100 ng/mL, 250 ng/mL, 500 ng/mL, and 1000 ng/mL bufalin. The authors observed significant displacement of digitoxin by bufalin as evidenced by increased free digitoxin concentrations. For example, the concentration of free digitoxin increased from a control value of 1.6 ng/mL to 2.5 ng/mL in the presence of 1000 ng/mL bufalin (total digitoxin: 36.3 ng/mL) in the serum pool 1. The authors observed similar increases in free digitoxin concentrations in other serum pools in the presence of various concentrations of bufalin. The authors used a chemiluminescent assay and ACS:180 analyzer to measure both total (in the original serum) and free (in the protein-free ultrafiltrate) digitoxin concentrations because the chemiluminescent assay does not cross-react with bufalin. When an acetone/water (1:1 by volume) extract of Chan Su was added to a serum pool containing digitoxin, the authors observed a significantly increased free digitoxin concentration, indicating that Chan Su can displace digitoxin from the protein binding site in vitro. The authors conclude that bufalin and acetone/water extract of Chan Su can cause significant displacement of digitoxin from the protein binding site.