Johnson J A, Livingston T N
Department of Clinical Pharmacy, University of Tennessee-Memphis 38163, USA.
Eur J Clin Pharmacol. 1997;51(6):485-8. doi: 10.1007/s002280050235.
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.
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.
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.
分别使用丙吡胺和水杨酸作为模型化合物，以表征α1-酸性糖蛋白（AGP）和白蛋白与药物结合的种族差异。从29名健康志愿者（15名白人，14名黑人）中采集无药物血浆。使用14C-丙吡胺和14C-水杨酸通过平衡透析法测定血浆中丙吡胺和水杨酸的未结合分数（fu）。
黑人中丙吡胺的未结合分数显著高于白人（0.131对0.113），水杨酸的未结合分数也是如此（0.053对0.048）。当对未结合分数进行AGP和白蛋白浓度校正后，种族差异不再存在。
许多与AGP和/或白蛋白结合的药物在未结合分数上可能表现出种族差异。然而，这些差异可能是由蛋白质浓度的差异而非蛋白质上结合位点数量的差异或蛋白质对药物亲和力的种族差异所解释。
