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Pilot Study of Isoniazid Acetylation in Melanesian Healthy Subject from Indonesia

机译:印度尼西亚美拉尼西亚健康受试者中异烟肼乙酰化的初步研究

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Objective: Isoniazid (INH) is metabolized by N-acetyl transferase-2 into acetyl isoniazid (Ac-INH). The acetylation rate is different in each ethnic, therefore it is very interesting to study of INH acetylation. The aims of this study were to synthesize Ac-INH and the produced Ac-INH was used as a working standard for the pilot study of INH acetylation in Melanesian healthy subjects from Indonesia. Methods: Ac-INH can be simply synthesized by acetylation reactions between INH and acetic anhydride. The synthesis results were characterized by organoleptic observation, purity test, UV-Vis spectrophotometry analysis, FTIR analysis, and mass spectrometry analysis. The pilot study of INH acetylation used high performance liquid chromatography to analyze the levels of INH and Ac-INH in blood of Melanesian healthy subjects. The acetylation rate of INH was determined by the ratio between Ac-INH and INH concentrations at 3 h after administration of INH. Results: The acetylation reaction to synthesize Ac-INH has been performed at temperature of 60°C for 30 min. The obtained Ac-INH had the same quality specifications with reference standard of Ac-INH. The average of ratio between of Ac-INH and INH concentrations was 1.5. The results showed that the six healthy subjects of Melanesians had slow acetylation. There was significant difference in the ratio between Ac-INH and INH concentrations in subjects (P0.05). Conclusion: The obtained Ac-INH could be used for pilot study of INH acetylation by calculating the ratio of Ac-INH and INH concentrations in plasma subject. The subject has to be increased to represent the Melanesian population from Indonesia.
机译:目的:异烟肼(INH)被N-乙酰基转移酶-2代谢为乙酰异烟肼(Ac-INH)。每个民族的乙酰化率都不同,因此研究INH乙酰化非常有趣。这项研究的目的是合成Ac-INH,并将产生的Ac-INH用作印度尼西亚Melanesian健康受试者INH乙酰化试验研究的工作标准。方法:通过INH与乙酸酐之间的乙酰化反应可以简单地合成Ac-INH。通过感官观察,纯度测试,UV-Vis分光光度法分析,FTIR分析和质谱分析来表征合成结果。 INH乙酰化的初步研究使用高效液相色谱法分析美拉尼西亚健康受试者血液中INH和Ac-INH的水平。 INH的乙酰化率由施用INH后3小时的Ac-INH与INH浓度之比确定。结果:在60℃的温度下进行了乙酰化反应以合成Ac-INH。所得Ac-INH具有与Ac-INH参考标准相同的质量规格。 Ac-INH和INH浓度之比的平均值小于1.5。结果表明,六名美拉尼西亚人的健康受试者乙酰化缓慢。 Ac-INH和INH浓度之间的比例存在显着差异(P <0.05)。结论:通过计算血浆中Ac-INH与INH浓度的比值,所得Ac-INH可用于INH乙酰化的初步研究。该主题必须增加以代表印度尼西亚的美拉尼西亚人口。

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