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巴拿马库纳美洲印第安人中司巴丁的氧化代谢:缺乏代谢缺陷者的证据

The oxidative metabolism of sparteine in the Cuna Amerindians of Panama: absence of evidence for deficient metabolizers.

作者信息

Arias T D, Jorge L F, Lee D, Barrantes R, Inaba T

机构信息

World Health Organization Center for Drug Quality Control, Instituto Especializado de Análisis, Panamá, República de Panamá.

出版信息

Clin Pharmacol Ther. 1988 Apr;43(4):456-65. doi: 10.1038/clpt.1988.58.

Abstract

Sparteine sulfate (50 mg) was administered to 170 Cuna Amerindians, 142 of whom were unrelated, and the drug and its dehydrometabolites were determined in the 0- to 12-hour urine samples. The log10 of the metabolic ratio was unimodally, but not normally, distributed and showed the following values: mean -0.21 +/- 0.26, median -0.24, limits -0.73 and 0.76, skewness 1.00, and kurtosis 4.95. On the basis of these results, it can be concluded that there are no deficient metabolizers in the Cuna sample population studied. However, the similarity of the skewness found between the Cuna sample population studied and the extensive Canadian white group, as well as an inflection point at 6.3 U in the former's probit plot, suggests the existence of at least two subgroups congregating within the same single mode in the frequency distribution curve. The use of the inflection point is discussed thoroughly, concluding that although it does not allow exclusion of the existence of genotypically different subgroups, the limitations of the data do not permit its use to determine the number of heterozygotes and thus the existence of polymorphism. The possibility of an isozyme variant, consistent with the general genetic structure of Amerindians, as suggested by the coexistence of two subgroups within the unimodal curve, is entertained.

摘要

向170名库纳美洲印第安人施用了硫酸金雀花碱(50毫克),其中142人无亲缘关系,并在0至12小时的尿液样本中测定了该药物及其脱氢代谢产物。代谢比的log10呈单峰分布,但不符合正态分布,其值如下:均值-0.21±0.26,中位数-0.24,范围-0.73至0.76,偏度1.00,峰度4.95。基于这些结果,可以得出结论,在所研究的库纳样本群体中不存在代谢缺陷者。然而,所研究的库纳样本群体与大量加拿大白人组之间发现的偏度相似性,以及前者概率图中6.3 U处的一个拐点,表明在频率分布曲线的同一单峰内至少存在两个亚组聚集。对拐点的使用进行了深入讨论,得出的结论是,虽然它不能排除存在基因型不同的亚组,但数据的局限性不允许用它来确定杂合子的数量,从而确定多态性的存在。考虑到单峰曲线内两个亚组共存所表明的与美洲印第安人一般遗传结构一致的同工酶变体的可能性。

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