Drug‐plasma protein binding in Kutchin Athapaskan Indians

Free fractions of diazepam (Dα), warfarin (Wα), and methadone (Mα) were measured in plasma obtained from 37 Kutchin Athapaskan Indians. Mean Dα (3.42%) varied directly with free fatty acid concentration (r = 0.65, P < 0.001) and was higher than previously found in other groups. These higher levels of fatty acids were associated with lower Wα (r = ‐0.43, P = 0.007), and Wα rose with time after a meal (r = 0.42, P = 0.01) when fatty acids usually fall. Mean Wα 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 Wα. Wα and Dα were inversely correlated (r = ‐0.33, P = 0.04), a result of the strong effects of fatty acids on these drugs. In contrast to both Dα and Wα, intersubject differences in Mα correlated inversely with α 1 ‐acid glycoprotein concentration (r = ‐0.50, P = 0.001), but not fatty acids. Clinical Pharmacology and Therapeutics (1982) 32 , 436–441; doi: 10.1038/clpt.1982.186