Musatti L, Maggi E, Moro E, Valzelli G, Tamassia V
J Int Med Res. 1981;9(5):381-6. doi: 10.1177/030006058100900515.
Two separate studies were performed: in the first study for healthy male volunteers received three single oral doses (150, 250 and 400 mg) of 5-methylpyrazine carboxylic acid 4-oxide (acipimox) according to a randomized sequence. Plasma levels of the drug were determined by RIA and urinary excretion by HPLC. In the second trial the effect of food on the drug bioavailability and pharmacokinetics during repeated administration was investigated in six volunteers. The RIA method was adopted to measure plasma and urine levels. Acipimox was rapidly and almost completely absorbed after the three single doses. About 90% of the administered dose was recovered as unchanges drug in urine collected up to 24 h. Peak plasma levels, area under plasma levels curves and urinary excretion were linearly related to the administered dose. The presence of food in the gastro-intestinal tract did not adversely affect the bioavailability of the drug. No significant changes were noted in the rate of elimination after 6 days of treatment with 250 mg t.i.d. Plasma levels determined after the 19th dose were in good agreement with those predicted on the assumption of linear pharmacokinetics and a one-compartment open model, with a half-life of about 2 h.
在第一项研究中，健康男性志愿者按照随机顺序接受了5 - 甲基吡嗪羧酸4 - 氧化物（阿西莫司）的三个单次口服剂量（150、250和400毫克）。通过放射免疫分析（RIA）测定药物的血浆水平，通过高效液相色谱法（HPLC）测定尿排泄量。在第二项试验中，在六名志愿者中研究了食物对重复给药期间药物生物利用度和药代动力学的影响。采用放射免疫分析方法测量血浆和尿液水平。在三个单次剂量给药后，阿西莫司迅速且几乎完全被吸收。在收集的长达24小时的尿液中，约90%的给药剂量以未变化的药物形式回收。血浆峰值水平、血浆水平曲线下面积和尿排泄量与给药剂量呈线性相关。胃肠道中食物的存在并未对药物的生物利用度产生不利影响。在用250毫克每日三次治疗6天后，消除速率未观察到显著变化。第19次给药后测定的血浆水平与基于线性药代动力学和单室开放模型假设预测的水平高度一致，半衰期约为2小时。
