Pharmacokinetic interaction study of ticagrelor and cyclosporine in healthy volunteers

Clin Drug Investig. 2014 Aug;34(8):529-36. doi: 10.1007/s40261-014-0205-2.


Background and objective: Patients with acute coronary syndrome and certain co-morbidities may receive ticagrelor, a reversibly binding P2Y(12) receptor antagonist, and cyclosporine, a commonly used immunosuppressant drug. This study assessed the potential pharmacokinetic drug-drug interaction between ticagrelor and cyclosporine.

Methods: In this single-centre, open-label, three-treatment, three-period crossover study (NCT01504906), healthy volunteers (n = 26) randomly received each of three treatments: cyclosporine (600 mg single oral dose) plus ticagrelor (180 mg single oral dose); cyclosporine alone; ticagrelor alone. Treatments were separated by a washout period of ≥14 days. Plasma concentrations of ticagrelor and its active metabolite (AR-C124910XX) and blood concentrations of cyclosporine were analyzed, and pharmacokinetic parameters were calculated. Safety and tolerability were assessed.

Results: Compared with ticagrelor alone, the geometric least squares mean (LSM) ratio (90 % confidence interval [CI]) for the ticagrelor area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) was 2.83 (2.63-3.06), and the maximum plasma concentration (C(max)) was 2.30 (2.06-2.58), in the presence of cyclosporine. Co-administration of cyclosporine with ticagrelor significantly increased AR-C124910XX AUC(∞) (1.33 [1.23-1.42]) and decreased C(max) (0.85 [0.76-0.94]). Ticagrelor had no effect on cyclosporine pharmacokinetic parameters, as the 90 % CIs of the LSM ratios were all within the 0.80-1.25 no-effect range. Co-administration of ticagrelor and cyclosporine was generally well tolerated.

Conclusion: Co-administration of cyclosporine with ticagrelor increased exposure to ticagrelor and its active metabolite and had no effect on cyclosporine pharmacokinetic parameters. The magnitude of cyclosporine's effect on ticagrelor pharmacokinetics does not warrant dose adjustment of ticagrelor.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacokinetics
  • Adult
  • Cross-Over Studies
  • Cyclosporine / pharmacokinetics*
  • Drug Interactions / physiology
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / pharmacokinetics*
  • Male
  • Purinergic P2Y Receptor Antagonists / pharmacokinetics*
  • Ticagrelor
  • Young Adult


  • Immunosuppressive Agents
  • Purinergic P2Y Receptor Antagonists
  • Cyclosporine
  • Ticagrelor
  • Adenosine

Associated data