Contribution of differences in plasma binding of propranolol to ethnic differences in sensitivity. Comparison between...

Chinese are more sensitive to the beta-blocking and hypotensive effects of propranolol than Caucasians. To determine the contribution of ethnic differences in the plasma binding of propranolol to the differences in sensitivity, 8 Caucasians (22.8 +/- 1.5 yr) and 8 Chinese (31.8 +/- 2.1 yr) were studied following single doses of 0, 10, 20, 40 and 80 mg propranolol orally. The binding of propranolol in plasma was determined by equilibrium dialysis after addition of 300 mg racemic propranolol to the plasma. The concentrations of free and bound (+) and (-)-propranolol were determined by stereospecific high performance liquid chromatography (HPLC). Dosage had no influence on the plasma binding of either enantiomer. The unbound fractions of both (-)-propranolol (16.06 +/- 0.79% vs 12.41 +/- 0.93%, P < 0.05) and (+)-propranolol (17.73 +/- 0.81% vs 14.33 +/- 0.89%, P < 0.01) were greater in Chinese than Caucasians, respectively. In both groups, the ratio of unbound (-) to (+)-propranolol was less than 1 (P < 0.01) and was greater in Chinese (0.91 +/- 0.01 vs 0.88 +/- 0.01) (P < 0.01), implying that in Chinese less isomers of both types were bound and there was a greater unbound proportion of the pharmacologically active (-)-propranolol which may contribute to their increased sensitivity to propranolol. It is demonstrated that ethnic differences in stereoselective protein binding may be an important variable in interindividual determinants of drug response.