Key result
Ticagrelor increases dabigatran AUC by ~7%, suggesting a limited pharmacokinetic interaction.
Why the study?
Combining dabigatran etexilate and ticagrelor increases bleeding risk, and research clarifying the pharmacokinetic drug-drug interaction between the two is scarce.
Does ticagrelor affect the pharmacokinetics of dabigatran etexilate in a PBPK model?
Does ticagrelor affect the pharmacokinetics of dabigatran etexilate in a PBPK model?
Effect estimate: 7.1% increase
PBPK modeling suggests ticagrelor only slightly increases dabigatran exposure, indicating pharmacokinetic interactions may not significantly limit their combined use.
Small exposure rise may not limit ticagrelor-dabigatran co-use; leaves open human validation.
Dabigatran etexilate (DABE) is a direct oral anticoagulant (DOAC) and may be combined with ticagrelor, a P2Y 12 inhibitor with antiplatelet effects. This combination of antiplatelet drugs and anticoagulants would increases the risk of bleeding in patients. In addition, the potential drug interaction may further increase the risk of bleeding. At present, there is scarce research to clarify the results of the interaction between the two. Therefore, we conducted this study to identify the potential impact of ticagrelor on the pharmacokinetics of DABE using physiologically based pharmacokinetic (PBPK) modeling. The models reasonably predicted the concentration-time profiles of dabigatran (DAB), the transformation form after DABE absorption, and ticagrelor. For pharmacokinetic drug-drug interaction (DDI), exposure to DAB at steady state was increased when co-administrated with ticagrelor. The C max and AUC 0-t of DAB were raised by approximately 8.7% and 7.1%, respectively. Meanwhile, a stable-state ticagrelor co-administration at 400 mg once-daily increased the C max and AUC 0-t of DAB by approximately 12.8% and 18.8%, respectively. As conclusions, Ticagrelor slightly increased the exposure of DAB. It is possible to safely use ticagrelor in a double or triple antithrombotic regimen containing DABE, only considering the antithrombotic efficacy, but not need to pay much attention on the pharmacokinetic DDI.
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Wang et al. (2020) studied Healthy volunteers (virtual). Ticagrelor vs. Dabigatran etexilate alone was evaluated on Dabigatran AUC0-t (7.1% increase). Ticagrelor co-administration slightly increased the steady-state Cmax and AUC0-t of dabigatran by approximately 8.7% and 7.1%, respectively, suggesting the pharmacokinetic interaction is limited.
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