title: Crushed Versus Integral Tablets of Ticagrelor in ST-Segment Elevation Myocardial Infarction Patients: A Randomized Pharmacokinetic/Pharmacodynamic Study.
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.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT02046486.
authors: Department of Cardiology, Patras University Hospital, Rion, 26500, Patras, Greece. dalex@med.upatras.gr.
authors: Dimitrios
authors: D
authors: Alexopoulos
authors: Department of Cardiology, Patras University Hospital, Rion, 26500, Patras, Greece.
authors: Nikolaos
authors: N
authors: Barampoutis
authors: Department of Cardiology, Patras University Hospital, Rion, 26500, Patras, Greece.
authors: Vasileios
authors: V
authors: Gkizas
authors: Department of Cardiology, Patras University Hospital, Rion, 26500, Patras, Greece.
authors: Chrysoula
authors: C
authors: Vogiatzi
authors: Department of Cardiology, Patras University Hospital, Rion, 26500, Patras, Greece.
authors: Grigorios
authors: G
authors: Tsigkas
authors: Department of Cardiology, Patras University Hospital, Rion, 26500, Patras, Greece.
authors: Nikolaos
authors: N
authors: Koutsogiannis
authors: Department of Cardiology, Patras University Hospital, Rion, 26500, Patras, Greece.
authors: Periklis
authors: P
authors: Davlouros
authors: Department of Cardiology, Patras University Hospital, Rion, 26500, Patras, Greece.
authors: George
authors: G
authors: Hahalis
authors: AstraZeneca R&D, Mölndal, Sweden.
authors: Sven
authors: S
authors: Nylander
authors: Cardiovascular and Thoracic Department, Careggi Hospital, Florence, Italy.
authors: Guido
authors: G
authors: Parodi
authors: Department of Cardiology, Patras University Hospital, Rion, 26500, Patras, Greece.
authors: Ioanna
authors: I
authors: Xanthopoulou
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D011187:Posture; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D016037:Single-Blind Method; D013607:Tablets; D000077486:Ticagrelor
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D013607:Tablets; D000077486:Ticagrelor; D000241:Adenosine