J A Johnson1, T N Livingston. 1. Department of Clinical Pharmacy, University of Tennessee-Memphis 38163, USA.
Abstract
OBJECTIVE: Disopyramide and salicylic acid were used as model compounds to characterize racial differences in binding of drugs by alpha 1-acid glycoprotein (AGP) and albumin, respectively. Drug-free plasma was collected from 29 healthy volunteers (15 white, 14 black). Disopyramide and salicylic acid unbound fractions (fu) in plasma were determined by equilibrium dialysis using 14C-disopyramide and 14C-salicylic acid. RESULTS: Disopyramide unbound fractions were significantly higher in blacks than whites (0.131 vs 0.113) as were salicylic acid unbound fractions (0.053 vs 0.048). When unbound fractions were corrected for AGP and albumin concentration, racial differences were no longer present. CONCLUSION: Many drugs which bind to AGP and/or albumin may exhibit racial differences in unbound fractions. However, these differences are likely explained by differences in protein concentrations rather than differences in the number of binding sites on the protein or racial differences in affinity of the protein for drugs.
OBJECTIVE:Disopyramide and salicylic acid were used as model compounds to characterize racial differences in binding of drugs by alpha 1-acid glycoprotein (AGP) and albumin, respectively. Drug-free plasma was collected from 29 healthy volunteers (15 white, 14 black). Disopyramide and salicylic acid unbound fractions (fu) in plasma were determined by equilibrium dialysis using 14C-disopyramide and 14C-salicylic acid. RESULTS:Disopyramide unbound fractions were significantly higher in blacks than whites (0.131 vs 0.113) as were salicylic acid unbound fractions (0.053 vs 0.048). When unbound fractions were corrected for AGP and albumin concentration, racial differences were no longer present. CONCLUSION: Many drugs which bind to AGP and/or albumin may exhibit racial differences in unbound fractions. However, these differences are likely explained by differences in protein concentrations rather than differences in the number of binding sites on the protein or racial differences in affinity of the protein for drugs.
Authors: Danny Tsai; Janattul-Ain Jamal; Joshua S Davis; Jeffrey Lipman; Jason A Roberts Journal: Clin Pharmacokinet Date: 2015-03 Impact factor: 6.447
Authors: Eric F Egelund; Marc Weiner; Rajendra P Singh; Thomas J Prihoda; Jonathon A L Gelfond; Hartmut Derendorf; William R Mac Kenzie; Charles A Peloquin Journal: Antimicrob Agents Chemother Date: 2014-05-19 Impact factor: 5.191
Authors: Ronald Kong; Oscar L Laskin; Diksha Kaushik; Fengbin Jin; Jiyuan Ma; Joseph McIntosh; Marcio Souza; Neil Almstead Journal: Clin Pharmacol Drug Dev Date: 2019-01-10
Authors: Anil R Maharaj; Daniel Gonzalez; Michael Cohen-Wolkowiez; Christoph P Hornik; Andrea N Edginton Journal: Clin Pharmacokinet Date: 2018-05 Impact factor: 5.577