Population Pharmacokinetic/Pharmacodynamic Models for P2Y12 Inhibitors: A Systematic Review and Clinical Appraisal Using Exposure Simulation

O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:e362-425.

PubMed  Google Scholar 

Kamran H, Jneid H, Kayani WT, Virani SS, Levine GN, Nambi V, Khalid U. Oral antiplatelet therapy after acute coronary syndrome: a review. JAMA. 2021;325:1545–55.

Article  CAS  PubMed  Google Scholar 

Mehran R, Pocock SJ, Stone GW, Clayton TC, Dangas GD, Feit F, Manoukian SV, Nikolsky E, Lansky AJ, Kirtane A, et al. Associations of major bleeding and myocardial infarction with the incidence and timing of mortality in patients presenting with non-ST-elevation acute coronary syndromes: a risk model from the ACUITY trial. Eur Heart J. 2009;30:1457–66.

Article  PubMed  PubMed Central  Google Scholar 

Xu X, Zhao X, Yang Z, Wang H, Meng X, Su C, et al. Significant Improvement of Metabolic Characteristics and Bioactivities of Clopidogrel and Analogs by Selective Deuteration. Molecules 2016;21(6):704.

Article  Google Scholar 

Dansette PM, Rosi J, Debernardi J, Bertho G, Mansuy D. Metabolic activation of prasugrel: nature of the two competitive pathways resulting in the opening of its thiophene ring. Chem Res Toxicol. 2012;25:1058–65.

Article  CAS  PubMed  Google Scholar 

Teng R, Oliver S, Hayes MA, Butler K. Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos Biol Fate Chem. 2010;38:1514–21.

Article  CAS  PubMed  Google Scholar 

Bergmark BA, Bhatt DL, Steg PG, Budaj A, Storey RF, Gurmu Y, Kuder JF, Im K, Magnani G, Oude Ophuis T, et al. Long-term ticagrelor in patients with prior coronary stenting in the PEGASUS-TIMI 54 trial. J Am Heart Assoc. 2021;10: e020446.

Article  PubMed  PubMed Central  Google Scholar 

Jones DW, Schermerhorn ML, Brooke BS, Conrad MF, Goodney PP, Wyers MC, Stone DH. Perioperative clopidogrel is associated with increased bleeding and blood transfusion at the time of lower extremity bypass. J Vasc Surg. 2017;65:1719-1728.e1711.

Article  PubMed  PubMed Central  Google Scholar 

Seese L, Sultan I, Gleason TG, Navid F, Wang Y, Kilic A. The impact of preoperative clopidogrel on outcomes after coronary artery bypass grafting. Ann Thorac Surg. 2019;108:1114–20.

Article  PubMed  Google Scholar 

Voetsch A, Pregartner G, Berghold A, Seitelberger R, Schoerghuber M, Toller W, Mahla E. How do type of preoperative P2Y(12) receptor inhibitor and withdrawal time affect bleeding? Ann Thorac Surg. 2021;111:77–84.

Article  PubMed  Google Scholar 

Neyens R, Donaldson C, Andrews C, Kellogg R, Spiotta A. Platelet function testing with a verifynow-directed personalized antiplatelet strategy and associated rates of thromboembolic complications after pipeline embolization for complex cerebral aneurysms. World Neurosurg. 2020;138:e674–82.

Article  PubMed  Google Scholar 

Patti G, Pasceri V, Vizzi V, Ricottini E, Di Sciascio G. Usefulness of platelet response to clopidogrel by point-of-care testing to predict bleeding outcomes in patients undergoing percutaneous coronary intervention (from the Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty-Bleeding Study). Am J Cardiol. 2011;107:995–1000.

Article  PubMed  Google Scholar 

Riesmeyer JS, Salazar DE, Weerakkody GJ, Ni L, Wrishko RE, Ernest CS 2nd, Luo J, Li YG, Small DS, Rohatagi S, Macias WL. Relationship between exposure to prasugrel active metabolite and clinical outcomes in the TRITON-TIMI 38 substudy. J Clin Pharmacol. 2012;52:789–97.

Article  CAS  PubMed  Google Scholar 

Small DS, Farid NA, Payne CD, Konkoy CS, Jakubowski JA, Winters KJ, Salazar DE. Effect of intrinsic and extrinsic factors on the clinical pharmacokinetics and pharmacodynamics of prasugrel. Clin Pharmacokinet. 2010;49:777–98.

Article  CAS  PubMed  Google Scholar 

Schilling U, Dingemanse J, Ufer M. Pharmacokinetics and pharmacodynamics of approved and investigational P2Y12 receptor antagonists. Clin Pharmacokinet. 2020;59:545–66.

Article  CAS  PubMed  Google Scholar 

Kim HS, Kang J, Hwang D, Han JK, Yang HM, Kang HJ, Koo BK, Rhew JY, Chun KJ, Lim YH, et al. Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (HOST-REDUCE-POLYTECH-ACS): an open-label, multicentre, non-inferiority randomised trial. Lancet (London, England). 2020;396:1079–89.

Article  CAS  PubMed  Google Scholar 

Saito S, Isshiki T, Kimura T, Ogawa H, Yokoi H, Nanto S, Takayama M, Kitagawa K, Nishikawa M, Miyazaki S, Nakamura M. Efficacy and safety of adjusted-dose prasugrel compared with clopidogrel in Japanese patients with acute coronary syndrome: the PRASFIT-ACS study. Circ J. 2014;78:1684–92.

Article  CAS  PubMed  Google Scholar 

Wang G, Wang X, Zhao G, Huang X, Guo R, Nie S. De-escalation of antiplatelet therapy after percutaneous coronary intervention among East Asians and non-East Asians: a meta-analysis of randomized controlled trials. BMC Cardiovasc Disord. 2022;22:29.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim HK, Tantry US, Smith SC Jr, Jeong MH, Park SJ, Kim MH, Lim DS, Shin ES, Park DW, Huo Y, et al. The East Asian Paradox: an updated position statement on the challenges to the current antithrombotic strategy in patients with cardiovascular disease. Thromb Haemost. 2021;121:422–32.

Article  PubMed  Google Scholar 

Dartois C, Brendel K, Comets E, Laffont CM, Laveille C, Tranchand B, Mentré F, Lemenuel-Diot A, Girard P. Overview of model-building strategies in population PK/PD analyses: 2002–2004 literature survey. Br J Clin Pharmacol. 2007;64:603–12.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Duan JZ. Applications of population pharmacokinetics in current drug labelling. J Clin Pharm Ther. 2007;32:57–79.

Article  CAS  PubMed  Google Scholar 

Mould DR, Upton RN. Basic concepts in population modeling, simulation, and model-based drug development. CPT Pharmacomet Syst Pharmacol. 2012;1: e6.

Article  CAS  Google Scholar 

Fuchs A, Csajka C, Thoma Y, Buclin T, Widmer N. Benchmarking therapeutic drug monitoring software: a review of available computer tools. Clin Pharmacokinet. 2013;52:9–22.

Article  CAS  PubMed  Google Scholar 

Gotta V, Widmer N, Montemurro M, Leyvraz S, Haouala A, Decosterd LA, Csajka C, Buclin T. Therapeutic drug monitoring of imatinib: Bayesian and alternative methods to predict trough levels. Clin Pharmacokinet. 2012;51:187–201.

Article  CAS  PubMed  Google Scholar 

Guidi M, Csajka C, Buclin T. Parametric approaches in population pharmacokinetics. J Clin Pharmacol. 2022;62:125–41.

Article  CAS  PubMed  Google Scholar 

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ (Clinical research ed). 2021;372: n71.

PubMed  Google Scholar 

Yang J, Qi G, Hu F, Zhang X, Xing Y, Wang P. Association between ticagrelor plasma concentration and bleeding events in Chinese patients with acute coronary syndrome. Br J Clin Pharmacol. 2022;88:4870–80.

Article  CAS  PubMed  Google Scholar 

Kirtane AJ, Parikh PB, Stuckey TD, Xu K, Witzenbichler B, Weisz G, Rinaldi MJ, Neumann FJ, Metzger DC, Henry TD, et al. Is there an ideal level of platelet P2Y12-receptor inhibition in patients undergoing percutaneous coronary intervention?: “Window” analysis from the ADAPT-DES Study (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents). JACC Cardiovasc Interv. 2015;8:1978–87.

Article  PubMed  Google Scholar 

Mahla E, Metzler H, Bornemann-Cimenti H, Prueller F, Raggam RB, Pregartner G, Berghold A, Baumann A, Goeroeg C, Gurbel PA. Platelet inhibition and bleeding in patients undergoing non-cardiac surgery-the BIANCA observational study. Thromb Haemost. 2018;118:864–72.

Article  PubMed  Google Scholar 

Lee J, Hwang Y, Kang W, Seong SJ, Lim MS, Lee HW, Yim DS, Sohn DR, Han S, Yoon YR. Population pharmacokinetic/pharmacodynamic modeling of clopidogrel in Korean healthy volunteers and stroke patients. J Clin Pharmacol. 2012;52:985–95.

Article  CAS  PubMed  Google Scholar 

Li J, Tang W, Storey RF, Husted S, Teng R. Population pharmacokinetics of ticagrelor in patients with acute coronary syndromes. Int J Clin Pharmacol Ther. 2016;54:666–74.

Article  PubMed  Google Scholar 

Röshammar D, Bergstrand M, Andersson T, Storey RF, Hamrén B. Population pharmacokinetics of ticagrelor and AR-C124910XX in patients with prior myocardial infarction. Int J Clin Pharmacol Ther. 2017;55:416–24.

Article  PubMed  Google Scholar 

Amilon C, Niazi M, Berggren A, Åstrand M, Hamrén B. Population pharmacokinetics/pharmacodynamics of ticagrelor in children with sickle cell disease. Clin Pharmacokinet. 2019;58:1295–307.

Article  CAS  PubMed  Google Scholar 

Jiang XL, Samant S, Lewis JP, Horenstein RB, Shuldiner AR, Yerges-Armstrong LM, Peletier LA, Lesko LJ, Schmidt S. Development of a physiology-directed population pharmacokinetic and pharmacodynamic model for characterizing the impact of genetic and demographic factors on clopidogrel response in healthy adults. Eur J Pharm Sci. 2016;82:64–78.

Article  CAS  PubMed  Google Scholar 

Ernest CS, Small DS, Rohatagi S, Salazar DE, Wallentin L, Winters KJ, Wrishko RE. Population pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in aspirin-treated patients with stable coronary artery disease. J Pharmacokinet Pharmacodyn. 2008;35:593–618.

Article  CAS  PubMed 

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