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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).

Yıl 2022, Cilt: 26 Sayı: 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

Öz

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.

Anahtar Kelimeler

Ticagrelor pharmacokinetics SECS TDM Gastroplus PBPK

Kaynakça

  • [1] Whalan. Lippincott® Illustrated Reviews: Pharmacology. South Asian Edition ed, India, 2002, pp.396–400
  • [2] Highlights of Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf
  • [3] Ticagrelor Monograph for Professionals. https://www.drugs.com/monograph/ticagrelor.html#uses
  • [4] RenliTeng, et al. Pharmacokinetic Profiles of Ticagrelor Orodispersible Tabletsin Healthy Western and Japanese Subjects. Clin Drug Investig. 2017, 37:1035–1045 [Crossref]
  • [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] 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] Nestorov . Whole-body physiologically based pharmacokineticmodels. Expert Opinion on Drug Metabolism & Toxicology 2007; 3 (2):235–249 [Crossref]
  • [8] https://www.Scifinder.com
  • [9] BrilintaTM (ticagrelor) Tablets. (2012). Pharmacy and Therapeutics, 37(4 section 2), pp.4–18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353491/
  • [10] Butler K, Teng R. Pharmacokinetics, pharmacodynamics, safety and tolerability of multiple ascending doses of ticagrelor in healthy volunteers. Br J ClinPharmacol. 2010;70:65–77 [Crossref]
  • [11] https://pubchem.ncbi.nlm.nih.gov/compound/Ticagrelor
  • [12] Adamski, P., Buszko, K., Sikora, J., Niezgoda, P., Barańska, M., Ostrowska, M., Paciorek, P., Navarese, E.P., Gorog, D.A. and Kubica, J. Metabolism of ticagrelor in patients with acute coronary syndromes. Scientific Reports, 2018, 8(1) [Crossref]
  • [13] Krakowiak, Alicja, et al. Ticagrelor-Related Severe Dyspnoea: Mechanisms, Characteristic Features, Differential Diagnosis and Treatment. Clinical Medicine Insights: Case Reports, vol. 13, Jan. 2020. [Crossref]
  • [14] Renli Teng. Ticagrelor: Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Profile: An Update. Clinical Pharmacokinetics,2015, vol. 54, no. 11,pp. 1125–1138 [Crossref]
  • [15] Bioanalytical Method Validation Guidance for Industry. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM) May 2018. https://www.fda.gov/files/drugs/published/Bioanalytical-Method-Validation-Guidance-for-Industry.pdf

Yıl 2022, Cilt: 26 Sayı: 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

Öz

Kaynakça

  • [1] Whalan. Lippincott® Illustrated Reviews: Pharmacology. South Asian Edition ed, India, 2002, pp.396–400
  • [2] Highlights of Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf
  • [3] Ticagrelor Monograph for Professionals. https://www.drugs.com/monograph/ticagrelor.html#uses
  • [4] RenliTeng, et al. Pharmacokinetic Profiles of Ticagrelor Orodispersible Tabletsin Healthy Western and Japanese Subjects. Clin Drug Investig. 2017, 37:1035–1045 [Crossref]
  • [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] 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] Nestorov . Whole-body physiologically based pharmacokineticmodels. Expert Opinion on Drug Metabolism & Toxicology 2007; 3 (2):235–249 [Crossref]
  • [8] https://www.Scifinder.com
  • [9] BrilintaTM (ticagrelor) Tablets. (2012). Pharmacy and Therapeutics, 37(4 section 2), pp.4–18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353491/
  • [10] Butler K, Teng R. Pharmacokinetics, pharmacodynamics, safety and tolerability of multiple ascending doses of ticagrelor in healthy volunteers. Br J ClinPharmacol. 2010;70:65–77 [Crossref]
  • [11] https://pubchem.ncbi.nlm.nih.gov/compound/Ticagrelor
  • [12] Adamski, P., Buszko, K., Sikora, J., Niezgoda, P., Barańska, M., Ostrowska, M., Paciorek, P., Navarese, E.P., Gorog, D.A. and Kubica, J. Metabolism of ticagrelor in patients with acute coronary syndromes. Scientific Reports, 2018, 8(1) [Crossref]
  • [13] Krakowiak, Alicja, et al. Ticagrelor-Related Severe Dyspnoea: Mechanisms, Characteristic Features, Differential Diagnosis and Treatment. Clinical Medicine Insights: Case Reports, vol. 13, Jan. 2020. [Crossref]
  • [14] Renli Teng. Ticagrelor: Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Profile: An Update. Clinical Pharmacokinetics,2015, vol. 54, no. 11,pp. 1125–1138 [Crossref]
  • [15] Bioanalytical Method Validation Guidance for Industry. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM) May 2018. https://www.fda.gov/files/drugs/published/Bioanalytical-Method-Validation-Guidance-for-Industry.pdf
Toplam 15 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık Bilimleri
Bölüm Articles
Yazarlar

Mohammed Khalil 0000-0002-1440-5792

Akram Al-saleh 0000-0002-0598-7268

Hana Makhamreh 0000-0003-0051-2607

Rabab Tayem 0000-0002-6066-1199

Mohammad Abufarah 0000-0001-5476-1719

Abdullah Zubi 0000-0001-8235-4694

Omaimah Najib 0000-0003-4388-6131

Mohammad Bader 0000-0001-9270-4600

Naji Najib 0000-0001-6291-5271

Suliman Alfayoumi 0000-0001-9372-8145

Nasir Idkaidek 0000-0003-3115-4240

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2022 Cilt: 26 Sayı: 5

Kaynak Göster

APA Khalil, M., Al-saleh, A., Makhamreh, H., Tayem, R., vd. (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.
AMA 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. Haziran 2025;26(5):1411-1419.
Chicago Khalil, Mohammed, Akram Al-saleh, Hana Makhamreh, Rabab Tayem, Mohammad Abufarah, Abdullah Zubi, Omaimah Najib, Mohammad Bader, Naji Najib, Suliman Alfayoumi, ve Nasir Idkaidek. “ 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, sy. 5 (Haziran 2025): 1411-19.
EndNote Khalil M, Al-saleh A, Makhamreh H, Tayem R, Abufarah M, Zubi A, Najib O, Bader M, Najib N, Alfayoumi S, Idkaidek N (01 Haziran 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 M. Khalil, “ Development of Physiologically-Based Pharmacokinetic (PBPK) Model and Validation of Class IV Drugs of Salivary Excretion Classification System (SECS)”., J. Res. Pharm., c. 26, sy. 5, ss. 1411–1419, 2025.
ISNAD Khalil, Mohammed vd. “ 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 (Haziran 2025), 1411-1419.
JAMA 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 vd. “ Development of Physiologically-Based Pharmacokinetic (PBPK) Model and Validation of Class IV Drugs of Salivary Excretion Classification System (SECS)”. Journal of Research in Pharmacy, c. 26, sy. 5, 2025, ss. 1411-9.
Vancouver 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(5):1411-9.