Biol. Pharm. Bull. 30(4) 826—829 (2007)

the Sand R-enantiomer, has been used as an anticoagulant agent. The anticoagulant activity of S-warfarin is 3—5 times as great as that of R-warfarin. Warfarin is highly bound to Site I, a warfarin binding site, in the human serum albumin (HSA) molecule (97—99%). The unbound fraction of warfarin is increased by the displacement of the binding site caused by the coadministration of several drugs. Impaired renal or liver function and hypoalbuminaemia also change the binding properties of warfarin to plasma proteins. Hence, albumin binding experiments using warfarin are frequently performed, but there are few reports about the effect of coadministered drugs on the stereoselective binding of warfarin to HSA. Ethanol is widely used as a pharmaceutical excipient for the solubilization of many hydrophobic drugs for injections. Although information about the effect of such excipients on the physicochemical stability of drugs in mixed injections are provided, there have been few studies about drug interaction with pharmaceutical excipients in the body after injection. Drug interactions with pharmaceutical excipients have reported in several studies, for example, that Cremophor EL and Tween 80 inhibit P-glycoprotein, and that Cremophor RH40 inhibits CYP3A. Pluronic F68 affects the binding to HSA of propranolol. Also, ethanol (0.1 to 10% (v/v) ; 17 to 1700 mM) affects the binding of warfarin to albumin but the effect of ethanol on the stereoselective binding was unknown. In addition, it was recently reported that an excipient changes the unbound fraction of naproxen, warfarin and digitoxin to commercial albumin preparations. Therefore, we studied the effect of ethanol on the stereoselective binding of warfarin enantiomers to HSA or commercial albumin preparations.