RACIAL-DIFFERENCES IN PROPRANOLOL ENANTIOMER KINETICS FOLLOWING SIMULTANEOUS IV AND ORAL-ADMINISTRATION

1 Racial differences in propranolol enantiomer kinetics following oral dosing were previously documented in our laboratory. The purpose of t his study was to more completely describe propranolol kinetics in blac k and white subjects with the goal of gaining a better understanding o f the mechanism(s) responsible for racial differences in oral proprano lol kinetics. 2 Twelve white and 13 black healthy males were included in the study. Poor metabolizers of dextromethorphan and mephenytoin we re excluded. Subjects took oral propranolol 80 mg every 8 h for 16 dos es and received an intravenous dose of radiolabelled propranolol with the 16th dose. Serum and urine samples were collected for 24 h after t he 16th dose. Serum concentrations of R- and S-propranolol and urine c oncentrations of its three primary metabolites were determined by h.p. l.c. 3 Apparent oral clearances of R- and S-propranolol were higher (P <0.05) in blacks than whites (R-propranolol: 5036 +/- 4175 ml min(-1) vs 2854 +/- 879 ml min(-1); S-propranolol 3255 +/- 1723 ml min(-1) vs 2125 +/- 510 mk min(-1); blacks vs whites). 4 R- and S-propranolol cle arances were higher in blacks than whites (R-propranolol 1069 +/- 316 ml min(-1) vs 841 +/- 161 ml min(-1); S-propranolol 947 +/- 271 ml min (-1) vs 771 +/- 142 ml min(-1); blacks us whites, P < 0.05). 5 There w ere trends (P>0.05<0.10) toward higher side chain oxidation, 4-hydroxy lation and R-propranolol glucuronidation in blacks compared with white s. Ethnic differences in the enantiomeric ratios of partial metabolic clearance values were not observed. 6 We conclude the higher propranol ol oral clearances in black subjects are explained by blacks having sl ightly higher hepatic metabolism via all three of its major metabolic pathways. Higher propranolol clearances among black subjects were also observed and we conclude this finding is explained largely by the hig her hepatic metabolism, but also by slightly higher liver blood flow a mong black subjects.