Racial differences in drug response. Altered sensitivity to and clearance of propranolol in men of Chinese descent as compared with American whites

Abstract

To determine whether the pharmacokinetics and pharmacodynamics of beta-blockade differ among racial groups, we gave 10 men of Chinese descent and 10 American white men 10, 20, 40, and 80 mg of propranolol every eight hours; the dosages were given in random order, and each dose was given for one day. The degree of beta-blockade was measured as the reduction in the heart rate and blood pressure in the supine and upright positions and during treadmill exercise testing. The Chinese subjects had at least a twofold greater sensitivity to the beta-blocking effects of propranolol than the white subjects, as indicated by the mean (+/- SEM) plasma concentrations producing a 20 percent reduction in the heart rate in both the supine position (197 +/- 31 vs. 536 +/- 58 nmol per liter; P less than 0.05) and the upright position (131 +/- 27 vs. 343 +/- 39 nmol per liter; P less than 0.05) and after exercise testing (96 +/- 12 vs. 185 +/- 23 nmol per liter; P less than 0.05). In addition, the Chinese subjects had much greater sensitivity to the hypotensive effects of propranolol, as shown by the concentrations that reduced blood pressure by 10 percent in the supine position (73 +/- 5 vs. 748 +/- 7 nmol per liter; P less than 0.01) and in the upright position (89 +/- 5 vs. 401 +/- 6 nmol per liter; P less than 0.01). No difference in beta-receptor density or affinity of lymphocytes was found between the groups. The Chinese group had a 45 percent higher free fraction of propranolol in plasma, which may have contributed to the increased drug effect but cannot explain it entirely. This group metabolized propranolol more rapidly than the white group, which resulted in a 76 percent higher clearance of an oral dose (3740 +/- 737 vs. 2125 +/- 214 ml per minute; P less than 0.05) because of increased metabolism through multiple metabolic pathways. We conclude that Chinese men have greater sensitivity than white men to the effects of propranolol on heart rate and blood pressure. Decreased protein binding may be responsible in part, but most of the effect remains to be explained.