Research Article

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).

Volume: 26 Number: 5 June 28, 2025
  • Mohammed Khalil
  • Akram Al-saleh
  • Hana Makhamreh
  • Rabab Tayem
  • Mohammad Abufarah
  • Abdullah Zubi
  • Omaimah Najib
  • Mohammad Bader
  • Naji Najib
  • Suliman Alfayoumi
  • Nasir Idkaidek *
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Journal of Research in Pharmacy
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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).

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

References

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  2. [2] Highlights of Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf
  3. [3] Ticagrelor Monograph for Professionals. https://www.drugs.com/monograph/ticagrelor.html#uses
  4. [4] RenliTeng, et al. Pharmacokinetic Profiles of Ticagrelor Orodispersible Tabletsin Healthy Western and Japanese Subjects. Clin Drug Investig. 2017, 37:1035–1045 [Crossref]
  5. [5] Idkaidek, N. and Arafat, T. Saliva versus plasma pharmacokinetics: Theory and application of a salivary excretion classification system. Molecular Pharmaceutics, 2012, 9(8), pp. 2358–2363. [Crossref]
  6. [6] Parkway, NuventraPharma Sciences2525 Meridian, and Suite 200 Durham. “What Is PBPK Modeling & Simulation in Drug Development?” PK / PD and Clinical Pharmacology Consultants, 9 Sept. 2020. https://www.nuventra.com/resources/blog/what-is-pbpk-modeling-simulation/
  7. [7] Nestorov . Whole-body physiologically based pharmacokineticmodels. Expert Opinion on Drug Metabolism & Toxicology 2007; 3 (2):235–249 [Crossref]
  8. [8] https://www.Scifinder.com

Details

Primary Language

English

Subjects

Pharmaceutical Sciences

Journal Section

Research Article

Authors

Mohammed Khalil This is me
0000-0002-1440-5792
Jordan

Mohammad Abufarah This is me
0000-0001-5476-1719
Jordan

Suliman Alfayoumi This is me
0000-0001-9372-8145
Jordan

Publication Date

June 28, 2025

Submission Date

March 25, 2022

Acceptance Date

April 14, 2022

Published in Issue

Year 2022 Volume: 26 Number: 5

IZ

https://izlik.org/JA99TC76WG

Cite

RIS / Bibtex
APA
Khalil, M., Al-saleh, A., Makhamreh, H., Tayem, R., Abufarah, M., Zubi, A., Najib, O., Bader, M., Najib, N., Alfayoumi, S., & Idkaidek, N. (2025). 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). Journal of Research in Pharmacy, 26(5), 1411-1419. https://izlik.org/JA99TC76WG
AMA
1.Khalil M, Al-saleh A, Makhamreh H, et al. 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). J. Res. Pharm. 2025;26(5):1411-1419. https://izlik.org/JA99TC76WG
Chicago
Khalil, Mohammed, Akram Al-saleh, Hana Makhamreh, et al. 2025. “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)”. Journal of Research in Pharmacy 26 (5): 1411-19. https://izlik.org/JA99TC76WG.
EndNote
Khalil M, Al-saleh A, Makhamreh H, Tayem R, Abufarah M, Zubi A, Najib O, Bader M, Najib N, Alfayoumi S, Idkaidek N (June 1, 2025) 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). Journal of Research in Pharmacy 26 5 1411–1419.
IEEE
[1]M. Khalil et al., “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)”., J. Res. Pharm., vol. 26, no. 5, pp. 1411–1419, June 2025, [Online]. Available: https://izlik.org/JA99TC76WG
ISNAD
Khalil, Mohammed - Al-saleh, Akram - Makhamreh, Hana - Tayem, Rabab - Abufarah, Mohammad - Zubi, Abdullah - Najib, Omaimah et al. “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)”. Journal of Research in Pharmacy 26/5 (June 1, 2025): 1411-1419. https://izlik.org/JA99TC76WG.
JAMA
1.Khalil M, Al-saleh A, Makhamreh H, Tayem R, Abufarah M, Zubi A, Najib O, Bader M, Najib N, Alfayoumi S, Idkaidek N. 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). J. Res. Pharm. 2025;26:1411–1419.
MLA
Khalil, Mohammed, et al. “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)”. Journal of Research in Pharmacy, vol. 26, no. 5, June 2025, pp. 1411-9, https://izlik.org/JA99TC76WG.
Vancouver
1.Mohammed Khalil, Akram Al-saleh, Hana Makhamreh, Rabab Tayem, Mohammad Abufarah, Abdullah Zubi, Omaimah Najib, Mohammad Bader, Naji Najib, Suliman Alfayoumi, Nasir Idkaidek. 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). J. Res. Pharm. [Internet]. 2025 Jun. 1;26(5):1411-9. Available from: https://izlik.org/JA99TC76WG