Pharmacosimulation of interruptions and its solution in intravenous administration of cangrelor.

BACKGROUND: Cangrelor is an intravenous adenosine diphosphate (ADP) P2Y(12) receptor antagonist, which has to be administered as a bolus followed by immediate infusion. Nevertheless, in clinical routine deviations from the correct practice, such as delayed infusion onset or interruptions during infusion, may occur. OBJECTIVE: The objective of the present study was to investigate the impact of administration delays on cangrelor concentration in a pharmacological simulation setting and to give possible solutions for the clinical practice. METHODS: We simulated the effects of different delays in administration of cangrelor in a model based on known pharmacokinetic parameters. Additionally, we calculated the optimal dosage of a second bolus. RESULTS: We demonstrate that already a short delay between the bolus and begin of infusion as well as short infusion interruptions considerably affect the serum concentration of cangrelor. Additionally, we estimate the dosage of a possible second bolus which highly depends on the duration of the delay. CONCLUSIONS: Our results emphasize that continuous administration of cangrelor is crucial to avoid the critical time frame of increased thrombosis risk. We suggest a strategy for dealing with interruptions by demonstrating that a second bolus allows to reach rapidly an effective but not excessive cangrelor serum concentration.