Advisor(s)
Dr. Eyob Adane: e-adane@onu.edu
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
Ticagrelor (Brilinta (R)) is the first reversibly binding oral P2Y12 receptor antagonist. It is used, mostly in combination with aspirin, in patients with acute coronary syndromes to reduce thrombosis. The manufacturer of ticagrelor recommends discontinuing it at least 5 days before any surgery when possible. While the effect of dose interruptions on the risk of thrombosis is not directly studied, it is important to understand the impact of skipping doses on ticagrelor's PK/PD profile for clinical-decision making. The objectives of the current study were to simulate the impact of therapy interruption on the PK/PD of ticagrelor and examine the need for loading dose administration when therapy is resumed. Population PK/PD parameters were based on data from the ONSET/OFFSET study and published in the literature. The PD of ticagrelor was described using a sigmoidal direct-response Imax model. A population PK/PD model describing the relationship between ticagrelor dose, plasma concentrations, and platelet inhibition was simulated with Simulx (Lixoft, France). Simulations were performed on 2000 patients by fixing PK parameters to their population estimates and allowing PD parameters to vary. The expected platelet inhibition was simulated after a loading dose of 180 mg followed by a maintenance dose of 90 mg twice daily for a 15-day course of treatment. Doses were stopped on day 8 for 0-5 days and treatment was resumed with or without a loading dose. Simulation results were evaluated for their potential to achieve a minimum of 80% platelet inhibition.
Key Words: Ticagrelor, P2Y12 receptor antagonist, Platelet inhibitions, Pharmacokinetics, Pharmacodynamics, Population PK/PD, Imax, Skipping dose
Recommended Citation
Matsui, Hiroyoshi; Pham, Le Thien Truc; and Adane, Eyob D., "Evaluating the Effect of Skipping Ticagrelor Doses and Need for Bolus Doses upon Treatment Resumption through Population PK/PD Simulation" (2024). ONU Student Research Colloquium. 37.
https://digitalcommons.onu.edu/student_research_colloquium/2024/Posters/37
Level of Access
Open Access
Open Access
Available to all.
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Cardiovascular Diseases Commons, Pharmacy and Pharmaceutical Sciences Commons, Statistical Models Commons, Surgery Commons
Evaluating the Effect of Skipping Ticagrelor Doses and Need for Bolus Doses upon Treatment Resumption through Population PK/PD Simulation
McIntosh Activities Room
Ticagrelor (Brilinta (R)) is the first reversibly binding oral P2Y12 receptor antagonist. It is used, mostly in combination with aspirin, in patients with acute coronary syndromes to reduce thrombosis. The manufacturer of ticagrelor recommends discontinuing it at least 5 days before any surgery when possible. While the effect of dose interruptions on the risk of thrombosis is not directly studied, it is important to understand the impact of skipping doses on ticagrelor's PK/PD profile for clinical-decision making. The objectives of the current study were to simulate the impact of therapy interruption on the PK/PD of ticagrelor and examine the need for loading dose administration when therapy is resumed. Population PK/PD parameters were based on data from the ONSET/OFFSET study and published in the literature. The PD of ticagrelor was described using a sigmoidal direct-response Imax model. A population PK/PD model describing the relationship between ticagrelor dose, plasma concentrations, and platelet inhibition was simulated with Simulx (Lixoft, France). Simulations were performed on 2000 patients by fixing PK parameters to their population estimates and allowing PD parameters to vary. The expected platelet inhibition was simulated after a loading dose of 180 mg followed by a maintenance dose of 90 mg twice daily for a 15-day course of treatment. Doses were stopped on day 8 for 0-5 days and treatment was resumed with or without a loading dose. Simulation results were evaluated for their potential to achieve a minimum of 80% platelet inhibition.
Key Words: Ticagrelor, P2Y12 receptor antagonist, Platelet inhibitions, Pharmacokinetics, Pharmacodynamics, Population PK/PD, Imax, Skipping dose