Drug-plasma protein binding in Kutchin Athapaskan indians

Free fractions of diazepam (D alpha), warfarin (W alpha), and methadone (M alpha) were measured in plasma obtained from 37 Kutchin Athapaskan Indians. Mean D alpha (3.42%) varied directly with free fatty acid concentration (r = 0.65, P less than 0.001) and was higher than previously found in other groups. These higher levels of fatty acids were associated with lower W alpha (r = -0.43, P = 0.007), and W alpha rose with time after a meal (r = 0.42, P = 0.01) when fatty acids usually fall. Mean W alpha was 0.72% and increased with age (r = 0.47, P = 0.004). In multivariate analysis, age, fatty acids, and time after the last meal together accounted for 42% of intersubject variation in W alpha. W alpha and D alpha were inversely correlated (r = -0.33, P = 0.04), a result of the strong effects of fatty acids in these drugs. In contrast to both D alpha and W alpha, intersubject differences in M alpha correlated inversely with alpha 1-acid glycoprotein concentration (r = -0.50, P = 0.001), but not fatty acids.