Advisor(s)
Eyob Adane, PhD, RPh, BCPS
Confirmation
1
Document Type
Poster
Location
McIntosh Activities Room
Start Date
19-4-2024 10:00 AM
End Date
19-4-2024 10:50 AM
Abstract
Background: Cangrelor (Kengreal(R) is a non-thienopyridine parenteral antiplatelet drug approved as an adjunct for the reduction of periprocedural myocardial infarction and stent thrombosis risk in patients undergoing percutaneous coronary intervention (PCI). It is also used off-label for bridging in patients who are off their antiplatelet agents prior to surgery. Cangrelor blocks the binding of adenosine diphosphate (ADP) by reversibly binding to P2Y12 receptors on platelet surfaces. In comparison to other P2Y12 antagonists, cangrelor has a rapidly reversible platelet inhibition effect with a short half-life of approximately 3-5 minutes. Data on simultaneous PK/PD modeling of cangrelor are, however, lacking. The aims of this study are, therefore, to propose a method for simultaneous PK/PD modeling and to simulate the PK/PD of alternative bolus and infusion doses of cangrelor. Methods: Plasma concentration versus time and pharmacodynamic response versus time data were extracted with PlotDigitizer from the publications of Akers et. al. (J Clin Pharmacol. 2010 Jan;50(1):27-35.) and Gelbenegger et. al. (Thromb J. 2022; 20: 19.), respectively. These data were used to generate 100 random samples at each time point from a log-normal distribution using R 4.2.3. These data would be simultaneously fit into a one-compartment pharmacokinetic model with linear elimination and a direct effect sigmoidal Imax model. Modeling and simulation would be performed to determine exposure and effect at various bolus and infusion doses of cangrelor using Monolix and Simulx (Lixoft, France). Results, Discussion & Conclusion: Pending
Keywords: Cangrelor, P2Y12 antagonist, non-thienopyridine, platelet inhibition, pharmacokinetics, pharmacodynamics, simulation
Recommended Citation
Pham, Le Thien Truc and Adane, Eyob, "Pharmacokinetic/Pharmacodynamic Modeling and Simulation of Various Bolus and Infusion Doses of Cangrelor" (2024). ONU Student Research Colloquium. 32.
https://digitalcommons.onu.edu/student_research_colloquium/2024/Posters/32
Level of Access
Open Access
Pharmacokinetic/Pharmacodynamic Modeling and Simulation of Various Bolus and Infusion Doses of Cangrelor
McIntosh Activities Room
Background: Cangrelor (Kengreal(R) is a non-thienopyridine parenteral antiplatelet drug approved as an adjunct for the reduction of periprocedural myocardial infarction and stent thrombosis risk in patients undergoing percutaneous coronary intervention (PCI). It is also used off-label for bridging in patients who are off their antiplatelet agents prior to surgery. Cangrelor blocks the binding of adenosine diphosphate (ADP) by reversibly binding to P2Y12 receptors on platelet surfaces. In comparison to other P2Y12 antagonists, cangrelor has a rapidly reversible platelet inhibition effect with a short half-life of approximately 3-5 minutes. Data on simultaneous PK/PD modeling of cangrelor are, however, lacking. The aims of this study are, therefore, to propose a method for simultaneous PK/PD modeling and to simulate the PK/PD of alternative bolus and infusion doses of cangrelor. Methods: Plasma concentration versus time and pharmacodynamic response versus time data were extracted with PlotDigitizer from the publications of Akers et. al. (J Clin Pharmacol. 2010 Jan;50(1):27-35.) and Gelbenegger et. al. (Thromb J. 2022; 20: 19.), respectively. These data were used to generate 100 random samples at each time point from a log-normal distribution using R 4.2.3. These data would be simultaneously fit into a one-compartment pharmacokinetic model with linear elimination and a direct effect sigmoidal Imax model. Modeling and simulation would be performed to determine exposure and effect at various bolus and infusion doses of cangrelor using Monolix and Simulx (Lixoft, France). Results, Discussion & Conclusion: Pending
Keywords: Cangrelor, P2Y12 antagonist, non-thienopyridine, platelet inhibition, pharmacokinetics, pharmacodynamics, simulation