O'Neil W M, Pezzullo J C, Di Girolamo A, Tsoukas C M, Wainer I W
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Br J Clin Pharmacol. 1999 Dec;48(6):811-8. doi: 10.1046/j.1365-2125.1999.00084.x.
To gauge the effect of disease state and disease progression on the glucuronidation and sulphation of paracetamol (APAP) among HIV-positive patients and patients with AIDS.
The extent of APAP glucuronidation and APAP sulphation was assessed using a spot urine sample collected 4 h after the oral administration of 500 mg of APAP to 108 patients with AIDS or HIV infection. The molar concentrations of APAP and its glucuronide and sulphate metabolites were determined using a validated h.p.l.c. method and glucuronidation and sulphation indices were constructed using APAP metabolite/APAP molar concentration ratios.
No effect of disease state, AIDS vs asymptomatic HIV positive vs control, on APAP glucuronidation or sulphation was observed. The patient population was studied over time and disease progression also did not significantly alter the calculated glucuronidation and sulphation indices. The effect of the concomitant administration of other therapeutic agents was assessed and in the cross sectional portion of the study dapsone appeared to significantly decrease APAP sulphation as did lamivudine. In the longitudinal portion of the study the latter effect was not observed but zidovudine was seen to increase APAP glucuronidation. The data also indicates that APAP glucuronidation may be reduced in patients who are >10% below their ideal body weight.
评估疾病状态和疾病进展对艾滋病病毒阳性患者及艾滋病患者体内对乙酰氨基酚(APAP)葡萄糖醛酸化和硫酸化的影响。
对108例艾滋病患者或艾滋病病毒感染者口服500毫克APAP后4小时采集的即时尿样进行检测,以评估APAP葡萄糖醛酸化和APAP硫酸化的程度。采用经过验证的高效液相色谱法测定APAP及其葡萄糖醛酸苷和硫酸盐代谢物的摩尔浓度,并使用APAP代谢物/APAP摩尔浓度比构建葡萄糖醛酸化和硫酸化指数。
未观察到疾病状态(艾滋病患者与无症状艾滋病病毒阳性患者与对照组)对APAP葡萄糖醛酸化或硫酸化有影响。对患者群体进行了长期研究,疾病进展也未显著改变计算得出的葡萄糖醛酸化和硫酸化指数。评估了同时服用其他治疗药物的影响,在研究的横断面部分,氨苯砜似乎显著降低了APAP硫酸化,拉米夫定也有同样作用。在研究的纵向部分未观察到后者的影响,但齐多夫定被发现可增加APAP葡萄糖醛酸化。数据还表明,实际体重低于理想体重10%以上的患者,其APAP葡萄糖醛酸化可能会降低。