Therapeutic Drug Monitoring of Ticagrelor in Jordanian Patients. Development of Physiologically-Based Pharmacokinetic (PBPK) Model and Validation of Class IV Drugs of Salivary Excretion Classification System (SECS).

Year 2022, Volume: 26 Issue: 5, 1411 - 1419, 28.06.2025

Mohammed Khalil Akram Al-saleh Hana Makhamreh Rabab Tayem Mohammad Abufarah Abdullah Zubi Omaimah Najib Mohammad Bader Naji Najib Suliman Alfayoumi Nasir Idkaidek

https://izlik.org/JA99TC76WG

Abstract

Ticagrelor is an orally administered antiplatelet agent that has been approved for the reduction of
cardiovascular risk in patients with history of cardiovascular disease. However, Ticagrelor can also cause adverse
effects, including dyspnea. Ticagrelor plasma and saliva concentrations of 63 Jordanian patients were measured using
a sensitive LCMS/MS method. Ticagrelor was not excreted in saliva as it corresponds to the Class IV salivary excretion
classification system. The correlation between plasma ticagrelor concentrations and the occurrence of dyspnea was
examined to establish a therapeutic window for plasma ticagrelor. A physiologically-based pharmacokinetic (PBPK)
model of ticagrelor was built and validated using previously- published plasma data. The validated model was then
used to predict the factors affecting ticagrelor plasma concentrations. A loading dose of 135 mg (1.5 tablet) instead of 2
tablets has been suggested to maintain its therapeutic effect and avoid dyspnea.

Keywords

Ticagrelor , pharmacokinetics , SECS , TDM , Gastroplus , PBPK

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