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

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 (C-max) and area under the plasma concentration-time curve from zero to infinity (AUC) by 23 % and 36 %, respectively. Simvastatin C-max and AUC were increased by 81 % and 56 % with ticagrelor. Ticagrelor also increased C-max 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 C-max 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.