Affiliations: [a] Department of Internal Medicine, Division of Cardiology, Pulmonary Diseases, Vascular Medicine, University Hospital Düsseldorf, Düsseldorf, Germany
| [b] Institute of Mathematical Modelling of Biological Systems, Department of Biology, Faculty of Mathematics and Natural Sciences, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| [c]
Max Planck Institute for Plant Breeding Research, Köln, Germany
Abstract: BACKGROUND:Cangrelor is an intravenous adenosine diphosphate (ADP) P2Y12 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.
