Effect of ethanol on the binding of warfarin enantiomers to human serum albumin.
Ethanol is widely used as a pharmaceutical excipient for the solubilization of many hydrophobic drugs for injections. However, there are only few studies about drug interaction with pharmaceutical excipients in the body after injection. In this study, the effect of ethanol (500 mM) or several alcohols (500 mM) on the stereoselective binding of warfarin enantiomers to fatty acid-free human serum albumin (HSA) or proteins of commercial albumin preparations was investigated. An ultrafiltration method was used for the separation of unbound warfarin enantiomers. By the addition of ethanol or 1-propanol, the unbound fraction of the S-enantiomer was decreased. On the other hand, the unbound fraction of the R-enantiomer was increased by the addition of ethanol or 1-propanol. Unbound fractions of both the S- and R-enantiomer were decreased by 2-propanol. In various commercial albumin preparations, unbound fractions of both the S- and R-enantiomer were increased by ethanol. The different effects of ethanol among fatty acid-free HSA and commercial albumin preparations were observed.
Tatsumi
Akitoshi
A
Department of Pharmaceutics, Kobe Pharmaceutical University, Japan. yktatua@hyo-med.ac.jp
Kadobayashi
Muneo
M
Iwakawa
Seigo
S
D002851:Chromatography, High Pressure Liquid; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D013237:Stereoisomerism; D014859:Warfarin / Q000097:blood / Q000737:chemistry / Q000378:metabolism*
D012709:Serum Albumin; D000431:Ethanol; D014859:Warfarin