Abstract
Objective
The objective of this study was to assess the pharmacokinetic and pharmacodynamic behavior of ticagrelor administered either as crushed (in the semi-upright sitting position) or as integral (in the supine position) tablets in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI).
Methods
We randomized 20 patients to ticagrelor 180 mg either as 2 integral tablets administered in the supine position (standard administration) or as 2 tablets crushed and dispersed, administered in the semi-upright sitting position. Blood samples were drawn for pharmacokinetic and pharmacodynamic assessment at randomization (0 h) and at 0.5, 1, 2, and 4 h.
Results
At 1 h, ticagrelor plasma exposure and area under the plasma concentration–time curve from time zero to 1 h (AUC1) (co-primary endpoints) were higher in the crushed versus integral tablets group (median 586 vs. 70.1 ng/mL and 234 vs. 24.4 ng·h/mL, respectively), with a ratio of adjusted geometric means (95 % confidence interval [CI]) of 12.67 (2.34–68.51) [p = 0.005] and 19.28 (3.51–106.06) [p = 0.002], respectively. Time to maximum plasma concentration was shorter in the crushed versus integral tablets group (median 2 vs. 4 h), with a ratio of adjusted geometric means (95 % CI) of 0.69 (0.49–0.97) [p = 0.035]. Parallel findings were observed with AR-C124910XX (active metabolite). Platelet reactivity (VerifyNow®) at 1 h was lower with crushed versus standard administration with least squares estimates mean difference (95 % CI) of 92 (−158.4 to 26.6) P2Y12 reaction units (p = 0.009).
Conclusions
In patients with STEMI undergoing primary PCI, ticagrelor crushed tablets administered in the semi-upright sitting position seems to lead to a faster—compared with standard administration—absorption, with stronger antiplatelet activity within the first hour.
Trial registration: ClinicalTrials.gov identifier: NCT02046486.
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Alexopoulos D. OraL crushed and dIspersed ticagrelor 180mg compared to whole tablets of eQUal dose in STEMI patients unDergoing primary PCI: a pharmacokinetic/pharmacodynamic study (the LIQUID Study) [ClinicalTrials.gov identifier NCT02046486]. US National Institutes of Health, ClinicalTrials.gov. https://www.clinicaltrials.gov. Accessed 6 Aug 2015.
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This study was supported by the Research Committee of the Patras University Medical School. Dr Alexopoulos has received speaker honoraria from AstraZeneca and Advisory Board fees from AstraZeneca, Boeringer Ingelheim, Bayer, and the Medicines Company. Dr Nylander is an employee of AstraZeneca. Dr Parodi has received consulting fees from Daiichi Sankyo, Eli Lilly, AstraZeneca, Bayer, and the Medicines Company and lecture fees from Daiichi Sankyo, Eli Lilly, and AstraZeneca. Nikolaos Barampoutis, Vasileios Gkizas, Chrysoula Vogiatzi, Grigorios Tsigkas, Nikolaos Koutsogiannis, Periklis Davlouros, George Hahalis, Sven Nylander, and Ioanna Xanthopoulou have nothing to disclose.
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Alexopoulos, D., Barampoutis, N., Gkizas, V. et al. Crushed Versus Integral Tablets of Ticagrelor in ST-Segment Elevation Myocardial Infarction Patients: A Randomized Pharmacokinetic/Pharmacodynamic Study. Clin Pharmacokinet 55, 359–367 (2016). https://doi.org/10.1007/s40262-015-0320-0
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DOI: https://doi.org/10.1007/s40262-015-0320-0