艾滋病患者氨苯砜不良反应与乙酰化表型和血浆／淋巴细胞谷胱甘肽浓度关系的研究

HIGH INCIDENCE OF ADVERSE DAPSONE REACTIONS IN AIDS PATIENTS RELATES TO SLOW ACETYLATOR PHENOTYPE AND TO LOW PLASMA/LYMPHOCYTE GLUTATHIONE LEVEL

对２１例接受氨苯砜治疗的艾滋病患者进行了乙酰化表型及血浆和淋巴细胞谷胱甘肽（ＧＳＨ）浓度测定。受试者６例快乙酰化表型个体中，仅１例有不良反应发生，为１７％。而１５例慢乙酰化表型个体中，７例有不良反应发生，为４６％。血浆和淋巴细胞ＧＳＨ浓度分别为６．９７±０．９５μｍ和２８．７５±２．７８ｎｍｏｌ／ｍｇ蛋白质，低于无不良反应患者（１０．９０±１．４４μｍ和３２．１５±２．２１ｎｍｏｌ／ｍｇ蛋白质）和健康对照者（１１．８５±１．８３μｍ和３３．７６±２．３２ｎｍｏｌ／ｍｇ蛋白质）。慢乙酰化表型者有较多的母体药物通过氧化代谢，使毒性代谢物氧化偶氮氨苯砜蓄积，发生不良反应。艾滋病患者ＧＳＨ消耗增加或参与ＧＳＨ合成的半胱氨酸缺乏，ＧＳＨ生成减少，机体解毒功能降低，进一步加剧不良反应。提示艾滋病患者慢乙酰化表型及血浆和淋巴细胞谷胱甘肽水平低下均导致较多的氨苯砜不良反应发生。

Twenty-one advanced AIDS patients(CD4<200/μl)are acetylate-phenotyped and their plasma and lymphocyte glutathione(GSH)concentrations are determined.1 of 6 rapid acetylators has adverse dapsone reactions(ADR),accounting for 17%,as compared with 46%for slow acetylators(7/15).Plasma or lymphocyte GSH level are 6.97±0. 95 μm and 28.75±2.78 nmol/mg protein for AIDS patients with adverse dapsone reactions, as compared with 10.90±1.44 μm and 32.15±2.21 nmol/mg protein for AIDS patients without adverse dapsone reactions and 11.85±1.83μm and 33. 76±2.32 nmol/mg protein for health controls.It can be concluded that slow acetylators are risk population of adverse dapsone reactions.The increased dapsone toxic metabolite,azoxydapsone,in slow acetylators and the depletion of GSH in AIDS patients might be responsible for its adverse reactions.Routine acetylate phenotyping is helpful in adjusting dosage regimen and in decreasing the adverse reactions of drugs acetylated in human body.