INTERETHNIC DIFFERENCES IN DRUG PROTEIN-BINDING AND ALPHA(1) ACID GLYCOPROTEIN CONCENTRATION

Interethnic differences in drug responsiveness may in part be accounte d for by differences in drug disposition. We investigated the reversib le binding interaction by equlibrium dialysis between a representative acidic (warfarin) and basic (lignocaine) drug and drug binding protei ns in 20 healthy age and sex matched Iranian and Irish (Caucasian) sub jects. The unbound fraction of warfarin and its major binding protein albumin, were similar in the two groups. In contrast unbound lignocain e was higher in Iranian subjects (49.6 +/- 6.96 vs 37.7 +/- 51%, mean +/- SD, p < 0.05) and this was associated with lower plasma concentrat ions of alpha(1) acid glycoprotein (AAG, 48.8 +/- 10 vs. 60.5 +/- 8 mg /dl p < 0.01) Such alterations may result in differences in drug respo nsiveness in addition to predictable pharmacokinetic consequences. Pro tein binding should be included in comparative studies of drugs in sub jects of different races.