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Reporting on Adverse Clinical Events

A randomized crossover study of 10 healthy volunteers (4 women and 6 men) was conducted to identify the increased plasma concentrations of ticagrelor with the intake of grapefruit juice. The mean age was 22 years. Participants ingested either 200 mL of grapefruit juice or water 3 times a day for 4 days. On day 3, they ingested a 90 mg dose of ticagrelor. Use of concurrent medications was prohibited for 1 week before and at least 72 hours after ticagrelor administration. The plasma concentrations of ticagrelor were measured using an API 3000 LC/MS/MS system, and the antiplatelet activity was tested with Verify Now P2Y12 assay. Grapefruit juice increased the Cmax of ticagrelor to 165% and it prolonged the half-life of ticagrelor from 6.7 to 7.2 hours. Grapefruit juice more than doubled the area under the curve of ticagrelor in all the subjects and enhanced antiplatelet effects. The authors concluded that grapefruit juice markedly increases plasma concentrations and antiplatelet effects of ticagrelor. Grapefruit juice inactivates the CYP3A4 enzyme in the intestinal wall, which inhibits the firstpass metabolism of ticagrelor causing increased concentrations. Ticagrelor [“Brilinta”] Holmberg MT et al (JT Backman, Department of Clinical Pharmacology, Helsinki University, Central Hospital, PO Box 705, FI-00029 HUS, Finland; e-mail: janne.backman@helsinki.fi) Grapefruit juice markedly increases the plasma concentration and antiplatelet effects of ticagrelor in healthy subjects [published online November 6, 2012]. Br J Clin Pharmacol. doi:10.1111/bcp.12026