Pharmacosimulation of interruptions and its solution in intravenous administration of cangrelor

Clin Hemorheol Microcirc. 2018;68(4):421-425. doi: 10.3233/CH-170323.

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.

Keywords: Cangrelor; P2Y12 inhibitor; pharmacokinetics; pharmacosimulation.

MeSH terms

  • Adenosine Monophosphate / administration & dosage
  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / pharmacology
  • Adenosine Monophosphate / therapeutic use
  • Administration, Intravenous / methods*
  • Female
  • Humans
  • Male
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use*

Substances

  • Platelet Aggregation Inhibitors
  • Adenosine Monophosphate
  • cangrelor