Differences in stereoselective disposition of propranolol do not explain sensitivity differences between white and Chinese subjects: correlation between the clearance of (-)- and (+)-propranolol.

We have previously demonstrated that Chinese subjects are more sensitive than white subjects to beta-blockade produced by propranolol. To determine if this difference was because a greater proportion of the total propranolol was the more active (-)-isomer of propranolol in the Chinese subjects than in the white subjects, the relative pharmacokinetics of (+)- and (-)-isomers of propranolol after administration of a single, 80 mg oral dose of racemic propranolol was studied in 10 Chinese male and in 9 white male healthy subjects. The plasma concentrations of both (+)- and (-)-propranolol were lower in Chinese than in white subjects, resulting in significantly lower peak plasma concentrations and areas under the concentration-time curve (AUC) in Chinese subjects, the half-life of elimination did not differ significantly between Chinese and white subjects or between the two isomers. The concentrations of the active (-)-propranolol were higher in both groups of subjects because of the lower clearance of the (-)-propranolol compared with the (+)-propranolol. An excellent correlation between the clearance of (+)- and (-)-propranolol was seen in the same individual. The ratio of AUC of (-)- and (+)-propranolol did not differ between Chinese subjects (0.64 +/- 0.03) and white subjects (0.71 +/- 0.09). The data suggest that the proportion of the two isomers found in Chinese and white subjects did not differ, and therefore differences in stereoselective disposition of propranolol cannot explain the increased sensitivity seen in Chinese individuals.