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European Journal of Clinical Pharmacology

, Volume 69, Issue 3, pp 477–487 | Cite as

Pharmacokinetic interaction studies of co-administration of ticagrelor and atorvastatin or simvastatin in healthy volunteers

  • Renli TengEmail author
  • Patrick D. Mitchell
  • Kathleen A. Butler
Pharmacokinetics and Disposition

Abstract

Purpose

Interactions between ticagrelor and atorvastatin or simvastatin were investigated in two-way crossover studies.

Methods

Both studies were open-label for statin; the atorvastatin study was placebo-controlled for ticagrelor. For atorvastatin, volunteers (n = 24) received ticagrelor (loading dose 270 mg; 90 mg twice daily, 7 days) or placebo, plus atorvastatin calcium (80 mg; day 5). For simvastatin, volunteers (n = 24) received simvastatin 80 mg, or ticagrelor (loading dose 270 mg; 180 mg twice daily, 7 days) plus simvastatin (80 mg; day 5). In each study, volunteers received the alternate treatment after washout (≥7 days).

Results

Ticagrelor increased mean atorvastatin maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from zero to infinity (AUC) by 23 % and 36 %, respectively. Simvastatin Cmax and AUC were increased by 81 % and 56 % with ticagrelor. Ticagrelor also increased Cmax and AUC of analysed atorvastatin metabolites by 13–55 % and 32–67 %, respectively, and simvastatin acid by 64 % and 52 %, respectively. Co-administration of ticagrelor with each statin was well tolerated.

Conclusions

Exposure to ticagrelor and its active metabolite, AR-C124910XX, was generally unchanged by a single dose of either statin, except for a minor increase in ticagrelor Cmax in the presence of simvastatin. Effects of ticagrelor on atorvastatin pharmacokinetics were modest and unlikely clinically relevant, while with simvastatin, changes were slightly larger, and simvastatin doses >40 mg with ticagrelor should be avoided.

Keywords

Ticagrelor AZD6140 Atorvastatin Simvastatin Co-administration Pharmacokinetics 

Notes

Acknowledgements

The authors would like to thank the principal investigators and the clinical research staff who took part in these studies. They also acknowledge the medical writing support by Patrick Hoggard (medical writer, Gardiner-Caldwell Communications, Macclesfield, UK). Funding to support this service was provided by AstraZeneca.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Renli Teng
    • 1
    Email author
  • Patrick D. Mitchell
    • 1
  • Kathleen A. Butler
    • 1
  1. 1.Clinical Pharmacology, AstraZeneca LP, OW3-117WilmingtonUSA

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