Quantitative Prediction of the Suppression of Drug-Induced Hemolysis by Cyclodextrins from Surface Tension Data
N. Funasaki, M. Ohigashi, S. Hada
1999
Citations
6
Citations
Journal
Journal name not available for this finding
Full text
Semantic Scholar
Key Takeaway Key Takeaway: Cyclodextrins effectively suppress drug-induced hemolysis by varying their binding constants and dimerization constants, with -CyD being the most effective for CPZ and -CyD for PB.
Abstract
The suppression of hemolysis induced with 0.7 mmol dm-3 chlorpromazine hydrochloride (CPZ) or 15 mmol dm-3 propantheline bromide (PB) by α-, β-, and γ-cyclodextrins (CyDs) is measured as a function of CyD concentration and is correlated with the surface tension of its solution determined at 310 K. The surface tension data allow us to estimate the 1:1 and 2:1 binding constants of CPZ with CyDs as well as the dimerization constant of CPZ. The 2:1 binding constant of CPZ with γ-CyD is larger than the 1:1 binding constant, whereas the converse result is observed for the PB−γ-CyD system. This cooperative binding of CPZ to γ-CyD would be ascribed to a higher tendency of CPZ to form dimer than that of PB. Both the capabilities of CyDs for hemolysis suppression and surface tension elevation are in the order β-CyD > γ-CyD > α-CyD for 0.7 mmol dm-3 CPZ, whereas those capabilities are in the order β-CyD ≈ γ-CyD > α-CyD for 15 mmol dm-3 PB. The bitter taste reduction and surface tension elevation for a 1.5 mmol dm-3 ...