title: Evaluation and characterization of the effects of ticagrelor on serum and urinary uric acid in healthy volunteers.
abstract: 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.
authors.affiliation: AstraZeneca LP, Wilmington, Delaware, USA.
authors.forename: K
authors.initials: K
authors.lastname: Butler
authors.forename: R
authors.initials: R
authors.lastname: Teng
mesh_terms: D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000328:Adult; D018592:Cross-Over Studies; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000139:chemically induced / Q000652:urine; D019271:Hypoxanthine / Q000097:blood; D008297:Male; D008875:Middle Aged; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077486:Ticagrelor; D013997:Time Factors; D014527:Uric Acid / Q000097:blood* / Q000652:urine*; D019820:Xanthine / Q000097:blood
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D019820:Xanthine; D014527:Uric Acid; D019271:Hypoxanthine; D000077486:Ticagrelor; D000241:Adenosine