Sirois P, Borgeat P, Lauzière M, Dubé L, Rubin P, Kesterson J
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, P.Q., Canada.
Agents Actions. 1991 Sep;34(1-2):117-20. doi: 10.1007/BF01993254.
The potency and reversibility of a new orally active 5-lipoxygenase (5-LO) inhibitor were evaluated in human volunteers. Zileuton (A-64077) 600 mg q.i.d. was administered to volunteers for 14 days in a phase I study, and blood samples were withdrawn, stimulated with ionophore A23187 and LTB4 levels were determined using both reverse phase high performance liquid chromatography (RP-HPLC) and radioimmunoassay (RIA). The drug significantly inhibited (above 70%) LTB4 biosynthesis in whole blood stimulated with A-23187 throughout the 14 days. The activity of 5-LO was also measured one week after stopping the medication and was returned to control levels. Measurement of LTB4 levels using either RP-HPLC or RIA gave similar percentage of inhibition although RIA appeared to underestimate by half the absolute amounts of LTB4 in the blood samples. These results show that Zileuton is a highly active and reversible 5-LO inhibitor in human.
在人类志愿者中评估了一种新型口服活性5-脂氧合酶（5-LO）抑制剂的效力和可逆性。在一项I期研究中，给志愿者服用齐留通（A-64077）600毫克，每日4次，持续14天，采集血样，用离子载体A23187刺激，并用反相高效液相色谱法（RP-HPLC）和放射免疫分析法（RIA）测定白三烯B4（LTB4）水平。在整个14天中，该药物显著抑制（超过70%）A-23187刺激的全血中LTB4的生物合成。停药一周后也测量了5-LO的活性，其恢复到对照水平。使用RP-HPLC或RIA测量LTB4水平得出的抑制百分比相似，尽管RIA似乎低估了血样中LTB4绝对量的一半。这些结果表明，齐留通在人体中是一种高活性且可逆的5-LO抑制剂。
