Pharmacokinetic interaction studies of co-administration of ticagrelor and atorvastatin or simvastatin in healthy volunteers
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Interactions between ticagrelor and atorvastatin or simvastatin were investigated in two-way crossover studies.
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).
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.
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.
KeywordsTicagrelor AZD6140 Atorvastatin Simvastatin Co-administration Pharmacokinetics
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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