AbstractThe interaction of propafenone enantiomers with human α1‐acid glycoprotein was studied using high‐performance liquid chromatography. Each of the two optical antipodes interacted with one class of high‐affinity binding sites characterized byKa(R)= (6.18 ± 0.93) × 105M−1, n(R)= 1.34 ± 0.09 for the (R)‐isomer andKa(S)= (8.93 ± 1.82) × 105M−1,n(S)= 0.99 ± 0.08 for the (S)‐isomer. Nonspecific binding to secondary low‐affinity high‐capacity binding site(s) was only slightly greater in the case of the (S)‐enantiomer (n′k′(S)= (1.06 ± 0.09) × 104M−1) compared to the (R)‐enantiomer (n′k′(R)= (6.87 ± 0.72) × 103M−1). It was concluded that both enantiomers interact with common single class of high‐affinity binding sites on AAG (along with nonspecific binding) exhibiting