AstraZeneca LP, Wilmington, Delaware, USA.
Clin Pharmacol Ther. 2012 Feb;91(2):264-71. doi: 10.1038/clpt.2011.223. Epub 2011 Dec 21.
During its development, ticagrelor, a drug designed to prevent thrombotic events in patients with acute coronary syndromes, was found to have an association with mild hyperuricemia. To investigate this effect further, we carried out a placebo-controlled, randomized, crossover study in 24 healthy male volunteers. The volunteers received ticagrelor (90 mg b.i.d. for 5 days), and serum uric acid and urinary uric acid excretion were assessed under strictly controlled conditions. After administration of ticagrelor, serum uric acid significantly increased (day 1: 4-6%; day 5: 4-10%) relative to placebo and rapidly returned to baseline after the last dose of the drug. Urinary uric acid excretion was significantly higher on day 1 (7%) and at 24-48 h after the morning dose on day 5 (17%) relative to placebo. Uric acid clearance was significantly higher 24-48 h after the morning dose on day 5 (11%). Uric acid fractional excretion was unaffected. Serum hypoxanthine and xanthine were elevated after multiple ticagrelor doses. No uric acid-related adverse events were seen. The study showed that ticagrelor-associated hyperuricemia is modest and reversible; serum uric acid elevation may have been caused by altered tubular secretion and/or increase in production.
在开发过程中，替格瑞洛是一种旨在预防急性冠脉综合征患者血栓事件的药物，被发现与轻度高尿酸血症有关。为了进一步研究这种作用，我们在 24 名健康男性志愿者中进行了一项安慰剂对照、随机、交叉研究。志愿者接受替格瑞洛（每天两次 90 毫克，连续 5 天）治疗，并在严格控制的条件下评估血清尿酸和尿尿酸排泄。与安慰剂相比，替格瑞洛给药后血清尿酸显著升高（第 1 天：4-6%；第 5 天：4-10%），并且在最后一次给药后迅速恢复到基线。与安慰剂相比，第 1 天（7%）和第 5 天早晨剂量后 24-48 小时（17%）尿尿酸排泄明显增加。第 5 天早晨剂量后 24-48 小时尿酸清除率显著升高（11%）。尿酸分数排泄不受影响。多次给予替格瑞洛后，血清次黄嘌呤和黄嘌呤升高。未观察到与尿酸相关的不良事件。该研究表明，替格瑞洛引起的高尿酸血症是适度和可逆的；血清尿酸升高可能是由于肾小管分泌改变和/或产生增加所致。
