K M Sowinski1, B S Burlew, J A Johnson. 1. Department of Clinical Pharmacy, Colleges of Pharmacy and Medicine, University of Tennessee, Memphis, USA.
Abstract
OBJECTIVE: Dose-response studies in patients with hypertension have shown that black subjects are less responsive to beta-blocker therapy than white subjects, whereas studies in healthy volunteers suggest marginal or no racial differences in response. No concentration-response studies have been conducted in black subjects and white subjects. The purpose of this study was to characterize beta-blocker pharmacodynamics in healthy black and white men. METHODS: Thirteen black and 13 white healthy men took 80 mg oral propranolol three times daily, for a total of 16 doses. Heart rate response to treadmill exercise was measured at various times over 24 hours. Serum propranolol samples were collected during the same 24-hour time period and were measured by chiral HPLC. The sigmoid maximal effect (Emax), Emax, and linear models were fitted to percentage reductions in exercise heart rate and S-propranolol concentrations. RESULTS: Black subjects had significantly lower values for serum concentration producing one-half the maximal effect (EC50) and unbound EC50 than white subjects (EC50: 10.2 ng/ml (4.4 to 28.0 ng/ml) versus 24.4 ng/ml (14.3 to 64.1 ng/ml), blacks versus whites; unbound EC50: 1.29 ng/ml (0.686 to 4.91 ng/ml) versus 2.77 ng/ml (1.70 to 8.11 ng/ml), blacks versus whites). There was no statistical difference in Emax (33.3% [22.2% to 39.7%] versus 38.3% [30.7% to 45.1%], blacks versus whites). CONCLUSIONS: Healthy black men were more sensitive to beta-blockade than healthy white men. The results of this study in healthy volunteers suggest that the racial differences in response observed in patients with hypertension are related to hypertensive pathophysiology rather than normal physiology.
OBJECTIVE: Dose-response studies in patients with hypertension have shown that black subjects are less responsive to beta-blocker therapy than white subjects, whereas studies in healthy volunteers suggest marginal or no racial differences in response. No concentration-response studies have been conducted in black subjects and white subjects. The purpose of this study was to characterize beta-blocker pharmacodynamics in healthy black and white men. METHODS: Thirteen black and 13 white healthy men took 80 mg oral propranolol three times daily, for a total of 16 doses. Heart rate response to treadmill exercise was measured at various times over 24 hours. Serum propranolol samples were collected during the same 24-hour time period and were measured by chiral HPLC. The sigmoid maximal effect (Emax), Emax, and linear models were fitted to percentage reductions in exercise heart rate and S-propranolol concentrations. RESULTS: Black subjects had significantly lower values for serum concentration producing one-half the maximal effect (EC50) and unbound EC50 than white subjects (EC50: 10.2 ng/ml (4.4 to 28.0 ng/ml) versus 24.4 ng/ml (14.3 to 64.1 ng/ml), blacks versus whites; unbound EC50: 1.29 ng/ml (0.686 to 4.91 ng/ml) versus 2.77 ng/ml (1.70 to 8.11 ng/ml), blacks versus whites). There was no statistical difference in Emax (33.3% [22.2% to 39.7%] versus 38.3% [30.7% to 45.1%], blacks versus whites). CONCLUSIONS: Healthy black men were more sensitive to beta-blockade than healthy white men. The results of this study in healthy volunteers suggest that the racial differences in response observed in patients with hypertension are related to hypertensive pathophysiology rather than normal physiology.
Authors: Daniel Kurnik; Chun Li; Gbenga G Sofowora; Eitan A Friedman; Mordechai Muszkat; Hong-Guang Xie; Paul A Harris; Scott M Williams; Usha B Nair; Alastair J J Wood; C Michael Stein Journal: Pharmacogenet Genomics Date: 2008-10 Impact factor: 2.089
Authors: Charles D Howell; Thomas C Dowling; Marika Paul; Abdus S Wahed; Norah A Terrault; Milton Taylor; Lennox Jeffers; Jay H Hoofnagle Journal: Clin Gastroenterol Hepatol Date: 2008-04-14 Impact factor: 11.382