Interethnic differences in drug protein binding and alpha 1 acid glycoprotein concentration.
Interethnic differences in drug responsiveness may in part be accounted for by differences in drug disposition. We investigated the reversible binding interaction by equilibrium dialysis between a representative acidic (warfarin) and basic (lignocaine) drug and drug binding proteins in 20 healthy age and sex matched Iranian and Irish (Caucasian) subjects. The unbound fraction of warfarin and its major binding protein albumin, were similar in the two groups. In contrast unbound lignocaine 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 concentrations 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 responsiveness in addition to predictable pharmacokinetic consequences. Protein binding should be included in comparative studies of drugs in subjects of different races.
Hosseine
S J
SJ
Department of Pharmacology & Therapeutics, Trinity College, Dublin, Ireland.
Farid
R
R
Ghalighi
M R
MR
Feely
J
J
D000293:Adolescent; D000328:Adult; D003431:Cross-Cultural Comparison; D005006:Ethnicity; D005260:Female; D006801:Humans; D007492:Iran; D007494:Ireland; D008012:Lidocaine / Q000493:pharmacokinetics*; D008297:Male; D009961:Orosomucoid / Q000378:metabolism*; D011485:Protein Binding; D012016:Reference Values; D014859:Warfarin / Q000493:pharmacokinetics*
D009961:Orosomucoid; D014859:Warfarin; D008012:Lidocaine