库钦阿萨巴斯卡印第安人的药物与血浆蛋白结合情况

Drug-plasma protein binding in Kutchin Athapaskan indians.

作者信息

Abel J G, Roth E A, Sellers E M, Ray A K

出版信息

Clin Pharmacol Ther. 1982 Oct;32(4):436-41. doi: 10.1038/clpt.1982.186.

DOI:10.1038/clpt.1982.186

Abstract

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.

摘要

在从37名库钦阿萨巴斯卡印第安人获取的血浆中，测定了地西泮（Dα）、华法林（Wα）和美沙酮（Mα）的游离分数。平均Dα（3.42%）与游离脂肪酸浓度呈正相关（r = 0.65，P < 0.001），且高于之前在其他群体中发现的水平。这些较高的脂肪酸水平与较低的Wα相关（r = -0.43，P = 0.007），并且在进食后脂肪酸通常下降时，Wα随时间上升（r = 0.42，P = 0.01）。平均Wα为0.72%，且随年龄增加（r = 0.47，P = 0.004）。在多变量分析中，年龄、脂肪酸和最后一餐之后的时间共同解释了Wα个体间变异的42%。Wα和Dα呈负相关（r = -0.33，P = 0.04），这是脂肪酸对这些药物产生强烈影响的结果。与Dα和Wα均不同，Mα的个体间差异与α1-酸性糖蛋白浓度呈负相关（r = -0.50，P = 0.001），但与脂肪酸无关。