Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Diabetes und Adipositas Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Clinical Pharmacokinetics
Erschienen in: Clinical Pharmacokinetics 5/2020

13.02.2020 | Review Article

Pharmacokinetics and Pharmacodynamics of Approved and Investigational P2Y12 Receptor Antagonists

verfasst von: Uta Schilling, Jasper Dingemanse, Mike Ufer

Erschienen in: Clinical Pharmacokinetics | Ausgabe 5/2020

Einloggen, um Zugang zu erhalten

Abstract

Coronary artery disease remains the major cause of mortality worldwide. Antiplatelet drugs such as acetylsalicylic acid and P2Y12 receptor antagonists are cornerstone treatments for the prevention of thrombotic events in patients with coronary artery disease. Clopidogrel has long been the gold standard but has major pharmacological limitations such as a slow onset and long duration of effect, as well as weak platelet inhibition with high inter-individual pharmacokinetic and pharmacodynamic variability. There has been a strong need to develop potent P2Y12 receptor antagonists with more favorable pharmacological properties. Prasugrel and ticagrelor are more potent and have a faster onset of action; however, they have shown an increased bleeding risk compared with clopidogrel. Cangrelor is highly potent and has a very rapid onset and offset of effect; however, its indication is limited to P2Y12 antagonist-naïve patients undergoing percutaneous coronary intervention. Two novel P2Y12 receptor antagonists are currently in clinical development, namely vicagrel and selatogrel. Vicagrel is an analog of clopidogrel with enhanced and more efficient formation of its active metabolite. Selatogrel is characterized by a rapid onset of action following subcutaneous administration and developed for early treatment of a suspected acute myocardial infarction. This review article describes the clinical pharmacology profile of marketed P2Y12 receptor antagonists and those under development focusing on pharmacokinetic, pharmacodynamic, and drug–drug interaction liability.
Literatur
1.
Naghavi M, Abajobir AA, Abbafati C, Abbas KM, Abd-Allah F, Abera SF, et al. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1151–210.
2.
Mangels DR, Nathan A, Tuteja S, Giri J, Kobayashi T. Contemporary antiplatelet pharmacotherapy in the management of acute coronary syndromes. Curr Treat Options Cardiovasc Med. 2018;20:17.PubMed
3.
Gachet C. P2Y12 receptors in platelets and other hematopoietic and non-hematopoietic cells. Purinergic Signal. 2012;8:609–19.PubMedPubMedCentral
4.
Dorsam RT, Kunapuli SP. Central role of the P2Y12 receptor in platelet activation. J Clin Investig. 2004;113:340–5.PubMed
5.
Cattaneo M. P2Y12 receptors: structure and function. J Thromb Haemost. 2015;13:S10–6.PubMed
6.
Tubaro M, Danchin N, Goldstein P, Filippatos G, Hasin Y, Heras M, et al. Pre-hospital treatment of STEMI patients: a scientific statement of the Working Group Acute Cardiac Care of the European Society of Cardiology. Acute Card Care. 2011;13:56–67.PubMed
7.
Amsterdam EA, Wenger NK, Brindis RG, Casey DE, Ganiats TG, Holmes DR, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary. Circulation. 2014;130:2354–94.PubMed
8.
Desager J-P. Clinical pharmacokinetics of ticlopidine. Clin Pharmacokinet. 1994;26:347–55.PubMed
9.
Zhang L, Lu J, Dong W, Tian H, Feng W, You H, et al. Meta-analysis of comparison of the newer P2Y12 inhibitors (oral preparation or intravenous) to clopidogrel in patients with acute coronary syndrome. J Cardiovasc Pharmacol. 2017;69:147–55.PubMed
10.
Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045–57.PubMed
11.
Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001–15.PubMed
12.
Fan Z-G, Zhang W-L, Xu B, Ji J, Tian N-L, He S-H. Comparisons between ticagrelor and clopidogrel following percutaneous coronary intervention in patients with acute coronary syndrome: a comprehensive meta-analysis. Drug Des Dev Ther. 2019;13:719–30.
13.
Kim K, Lee TA, Touchette DR, DiDomenico RJ, Ardati AK, Walton SM. Contemporary trends in oral antiplatelet agent use in patients treated with percutaneous coronary intervention for acute coronary syndrome. J Manag Care Spec Pharm. 2017;23:57–63.PubMed
14.
15.
16.
17.
18.
Basra SS, Wang TY, Simon DJN, Chiswell K, Virani SS, Alam M, et al. Ticagrelor use in acute myocardial infarction: insights from the National Cardiovascular Data Registry. J Am Heart Assoc. 2018;7:1–11.
19.
Yudi MB, Clark DJ, Farouque O, Eccleston D, Andrianopoulos N, Duffy SJ, et al. Clopidogrel, prasugrel or ticagrelor in patients with acute coronary syndromes undergoing percutaneous coronary intervention. Intern Med J. 2016;46:559–65.PubMed
20.
Angerås O, Hasvold P, Thuresson M, Deleskog A, ÖBraun O. Treatment pattern of contemporary dual antiplatelet therapies after acute coronary syndrome: a Swedish nationwide population-based cohort study. Scand Cardiovasc J. 2016;50:99–107.PubMed
21.
Esteve-Pastor MA, Ruíz-Nodar JM, Orenes-Piñero E, Rivera-Caravaca JM, Quintana-Giner M, Véliz-Martínez A, et al. Temporal trends in the use of antiplatelet therapy in patients with acute coronary syndromes. J Cardiovasc Pharmacol Ther. 2018;23:57–65.PubMed
22.
23.
24.
Savi P, Herbert JM, Pflieger AM, Dol F, Delebassee D, Combalbert J, et al. Importance of hepatic metabolism in the antiaggregating activity of the thienopyridine clopidogrel. Biochem Pharmacol. 1992;44:527–32.PubMed
25.
Taubert D, von Beckerath N, Grimberg G, Lazar A, Jung N, Goeser T, et al. Impact of P-glycoprotein on clopidogrel absorption. Clin Pharmacol Ther. 2006;80:486–501.PubMed
26.
Tang M, Mukundan M, Yang J, Charpentier N, LeCluyse EL, Black C, et al. Antiplatelet agents aspirin and clopidogrel are hydrolyzed by distinct carboxylesterases, and clopidogrel Is transesterificated in the presence of ethyl alcohol. J Pharmacol Exp Ther. 2006;319:1467–76.PubMed
27.
Hagihara K, Kazui M, Kurihara A, Yoshiike M, Honda K, Okazaki O, et al. A possible mechanism for the differences in efficiency and variability of active metabolite formation from thienopyridine antiplatelet agents, prasugrel and clopidogrel. Drug Metab Dispos. 2009;37:2145–52.PubMed
28.
Neuvonen M, Tarkiainen EK, Tornio A, Hirvensalo P, Tapaninen T, Paile-Hyvärinen M, et al. Effects of genetic variants on carboxylesterase 1 gene expression, and clopidogrel pharmacokinetics and antiplatelet effects. Basic Clin Pharmacol Toxicol. 2018;122:341–5.PubMed
29.
Savi P, Pereillo JM, Uzabiaga MF, Combalbert J, Picard C, Maffrand JP, et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost. 2000;84:891–6.PubMed
30.
Tuffal G, Roy S, Lavisse M, Brasseur D, Schofield J, Delesque Touchard N, et al. An improved method for specific and quantitative determination of the clopidogrel active metabolite isomers in human plasma. Thromb Haemost. 2011;105:696–705.PubMed
31.
Pereillo JM, Maftouh M, Andrieu A, Uzabiaga MF, Fedeli O, Savi P, et al. Structure and stereochemistry of the active metabolite of clopidogrel. Drug Metab Dispos. 2002;30:1288–95.PubMed
32.
Kazui M, Nishiya Y, Ishizuka T, Hagihara K, Farid NA, Okazaki O, et al. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos. 2010;38:92–9.PubMed
33.
Farid NA, Kurihara A, Wrighton SA. Metabolism and disposition of the thienopyridine antiplatelet drugs ticlopidine, clopidogrel, and prasugrel in humans. J Clin Pharmacol. 2010;50:126–42.PubMed
34.
Brandt JT, Close SL, Iturria SJ, Payne CD, Farid NA, Ernest CS, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J Thromb Haemost. 2007;5:2429–36.PubMed
35.
Dansette PM, Rosi J, Bertho G, Mansuy D. Cytochromes P450 catalyze both steps of the major pathway of clopidogrel bioactivation, whereas paraoxonase catalyzes the formation of a minor thiol metabolite isomer. Chem Res Toxicol. 2012;25:348–56.PubMed
36.
Mega JLL, Close SLL, Wiviott SDD, Shen L, Hockett RDD, Brandt JTT, et al. Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360:354–62.PubMed
37.
Bouman HJ, Schömig E, Van Werkum JW, Velder J, Hackeng CM, HirschhÄuser C, et al. Paraoxonase-1 is a major determinant of clopidogrel efficacy. Nat Med. 2011;17:110–6.PubMed
38.
Ford NF. The metabolism of clopidogrel: CYP2C19 is a minor pathway. J Clin Pharmacol. 2016;56:1474–83.PubMed
39.
Ford NF, Taubert D. Clopidogrel, CYP2C19, and a black box. J Clin Pharmacol. 2013;53:241–8.PubMed
40.
Jiang X-L, Samant S, Lewis JP, Horenstein RB, Shuldiner AR, Yerges-Armstrong LM, et al. 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.PubMed
41.
Ernest CS 2nd, Small DS, Rohatagi S, Salazar DE, Wallentin L, Winters KJ, et al. Population pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in aspirin-treated patients with stable coronary artery disease. J Pharmacokinet Pharmacodyn. 2008;35:593–618.PubMed
42.
Danielak D, Karaźniewicz-Łada M, Komosa A, Burchardt P, Lesiak M, Kruszyna Ł, et al. Influence of genetic co-factors on the population pharmacokinetic model for clopidogrel and its active thiol metabolite. Eur J Clin Pharmacol. 2017;73:1623.PubMedPubMedCentral
43.
Lee J, Hwang Y, Kang W, Seong SJ, Lim M, Lee HW, et al. Population pharmacokinetic/pharmacodynamic modeling of clopidogrel in Korean healthy volunteers and stroke patients. J Clin Pharmacol. 2012;52:985–95.PubMed
44.
Danese E, Fava C, Beltrame F, Tavella D, Calabria S, Benati M, et al. Relationship between pharmacokinetics and pharmacodynamics of clopidogrel in patients undergoing percutaneous coronary intervention: comparison between vasodilator-stimulated phosphoprotein phosphorylation assay and multiple electrode aggregometry. J Thromb Haemost. 2016;14:282–93.PubMed
45.
Small DS, Farid NA, Li YG, Steven Ernest C II, Payne CD, Salazar DE, et al. Effect of ranitidine on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel. Curr Med Res Opin. 2008;24:2251–7.PubMed
46.
Frelinger AL 3rd, Bhatt DL, Lee RD, Mulford DJ, Wu J, Nudurupati S, et al. Clopidogrel pharmacokinetics and pharmacodynamics vary widely despite exclusion or control of polymorphisms (CYP2C19, ABCB1, PON1), noncompliance, diet, smoking, co-medications (including proton pump inhibitors), and pre-existent variability in platelet f. J Am Coll Cardiol. 2013;61:872–9.PubMed
47.
Payne CD, Li YG, Small DS, Ernest CS, Farid NA, Jakubowski JA, et al. Increased active metabolite formation explains the greater platelet inhibition with prasugrel compared to high-dose clopidogrel. J Cardiovasc Pharmacol. 2007;50:555–62.PubMed
48.
Taubert D, Kastrati A, Harlfinger S, Gorchakova O, Lazar A, von Beckerath N, et al. Pharmacokinetics of clopidogrel after administration of a high loading dose. Thromb Haemost. 2004;92:311–6.PubMed
49.
Lins R, Broekhuysen J, Necciari J, Deroubaix X. Pharmacokinetic profile of 14C-labeled clopidogrel. Semin Thromb Hemost. 1999;25(Suppl. 2):29–33.PubMed
50.
von Beckerath N, Taubert D, Pogatsa-Murray G, Schömig E, Kastrati A, Schömig A, et al. Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE (intracoronary stenting and antithrombotic regimen: choose between 3 high oral doses for immediate clopidogrel effect). Circulation. 2005;112:2946–50.
51.
Collet J-P, Hulot J-S, Anzaha G, Pena A, Chastre T, Caron C, et al. High doses of clopidogrel to overcome genetic resistance. JACC Cardiovasc Interv. 2011;4:392–402.PubMed
52.
Horenstein RB, Madabushi R, Zineh I, Yerges-Armstrong LM, Peer CJ, Schuck RN, et al. Effectiveness of clopidogrel dose escalation to normalize active metabolite exposure and antiplatelet effects in CYP2C19 poor metabolizers. J Clin Pharmacol. 2014;54:865–73.PubMedPubMedCentral
53.
Li YG, Ni L, Brandt JT, Small DS, Payne CD, Ernest CS, et al. Inhibition of platelet aggregation with prasugrel and clopidogrel: an integrated analysis in 846 subjects. Platelets. 2009;20:316–27.PubMed
54.
Thebault JJ, Kieffer G, Cariou R. Single-dose pharmacodynamics of clopidogrel. Semin Thromb Hemost. 1999;25(Suppl. 2):3–8.PubMed
55.
Authors/Task Force Members, Windecker S, Kolh P, Alfonso F, Collet J-P, Cremer J, et al. ESC/EACTS guidelines on myocardial revascularization. Eur Heart J. 2014;2014(35):2541–619.
56.
Oliphant CS, Trevarrow BJ, Dobesh PP. Clopidogrel response variability: review of the literature and practical considerations. J Pharm Pract. 2016;29:26–34.PubMed
57.
Gurbel PA, Becker RC, Mann KG, Steinhubl SR, Michelson AD. Platelet function monitoring in patients with coronary artery disease. J Am Coll Cardiol. 2007;50:1822–34.PubMed
58.
Gurbel PA, Tantry US. Drug insight: clopidogrel nonresponsiveness. Nat Clin Pract Cardiovasc Med. 2006;3:387–95.PubMed
59.
Farid NA, Smith RL, Gillespie TA, Rash TJ, Blair PE, Kurihara A, et al. The disposition of prasugrel, a novel thienopyridine, in humans. Drug Metab Dispos. 2007;35:1096–104.PubMed
60.
Williams ET, Jones KO, Ponsler GD, Lowery SM, Perkins EJ, Wrighton SA, et al. The biotransformation of prasugrel, a new thienopyridine prodrug, by the human carboxylesterases 1 and 2. Drug Metab Dispos. 2008;36:1227–32.PubMed
61.
Kurokawa T, Fukami T, Yoshida T, Nakajima M. Arylacetamide deacetylase is responsible for activation of prasugrel in human and dog. Drug Metab Dispos. 2016;44:409–16.PubMed
62.
Rehmel JLF, Eckstein JA, Farid NA, Heim JB, Kasper SC, Kurihara A, et al. Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet agent, with the cytochromes P450. Drug Metab Dispos. 2006;34:600–7.PubMed
63.
Small DS, Li YG, Ernest CS, April JH, Farid NA, Payne CD, et al. Integrated analysis of pharmacokinetic data across multiple clinical pharmacology studies of prasugrel, a new thienopyridine antiplatelet agent. J Clin Pharmacol. 2011;51:321–32.PubMed
64.
Matsushima N, Jakubowski JA, Asai F, Naganuma H, Brandt JT, Hirota T, et al. Platelet inhibitory activity and pharmacokinetics of prasugrel (CS-747) a novel thienopyridine P2Y12 inhibitor: a multiple-dose study in healthy humans. Platelets. 2006;17:218–26.PubMed
65.
Sugidachi A, Ogawa T, Kurihara A, Hagihara K, Jakubowski JA, Hashimoto M, et al. The greater in vivo antiplatelet effects of prasugrel as compared to clopidogrel reflect more efficient generation of its active metabolite with similar antiplatelet activity to that of clopidogrel’s active metabolite. J Thromb Haemost. 2007;5:1545–51.PubMed
66.
Brandt JT, Payne CD, Wiviott SD, Weerakkody G, Farid NA, Small DS, et al. A comparison of prasugrel and clopidogrel loading doses on platelet function: magnitude of platelet inhibition is related to active metabolite formation. Am Heart J. 2007;153(66):e9–16.
67.
Wallentin L, Varenhorst C, James S, Erlinge D, Braun OO, Jakubowski JA, et al. Prasugrel achieves greater and faster P2Y12 receptor-mediated platelet inhibition than clopidogrel due to more efficient generation of its active metabolite in aspirin-treated patients with coronary artery disease. Eur Heart J. 2007;29:21–30.PubMed
68.
Jakubowski JA, Payne CD, Weerakkody GJ, Brandt JT, Farid NA, Li YG, et al. Dose-dependent inhibition of human platelet aggregation by prasugrel and its interaction with aspirin in healthy subjects. J Cardiovasc Pharmacol. 2007;49:167–73.PubMed
69.
Husted S, Van Giezen JJJ. Ticagrelor: the first reversibly binding oral p2y12 receptor antagonist. Cardiovasc Ther. 2009;27:259–74.PubMedPubMedCentral
70.
Van Giezen JJ, Nilsson L, Berntsson P, Wissing BM, Giordanetto F, Tomlinson W, et al. Ticagrelor binds to human P2Y(12) independently from ADP but antagonizes ADP-induced receptor signaling and platelet aggregation. J Thromb Haemost. 2009;7:1556–65.
71.
Teng R, Maya J. Absolute bioavailability and regional absorption of ticagrelor in healthy volunteers. J Drug Assess. 2014;3:43–50.PubMedPubMedCentral
72.
Teng R, Oliver S, Hayes MA, Butler K. Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos. 2010;38:1514–21.PubMed
73.
Teng R, Butler K. Pharmacokinetics, pharmacodynamics, tolerability and safety of single ascending doses of ticagrelor, a reversibly binding oral P2Y12 receptor antagonist, in healthy subjects. Eur J Clin Pharmacol. 2010;66:487–96.PubMed
74.
Adamski P, Buszko K, Sikora J, Niezgoda P, Barańska M, Ostrowska M, et al. Metabolism of ticagrelor in patients with acute coronary syndromes. Sci Rep. 2018;8:11746.PubMedPubMedCentral
75.
Teng R. Pharmacokinetic, pharmacodynamic and pharmacogenetic profile of the oral antiplatelet agent ticagrelor. Clin Pharmacokinet. 2012;51:305–18.PubMed
76.
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.PubMed
77.
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.PubMed
78.
Åstrand M, Amilon C, Röshammar D, Himmelmann A, Angiolillo DJ, Storey RF, et al. Pharmacokinetic-pharmacodynamic modelling of platelet response to ticagrelor in stable coronary artery disease and prior myocardial infarction patients. Br J Clin Pharmacol. 2018;1–9.
79.
Liu S, Xue L, Shi X, Sun Z, Zhu Z, Zhang X, et al. Population pharmacokinetics and pharmacodynamics of ticagrelor and AR-C124910XX in Chinese healthy male subjects. Eur J Clin Pharmacol. 2018;74:745–54.PubMed
80.
Teng R, Mitchell P, Butler K. Effect of rifampicin on the pharmacokinetics and pharmacodynamics of ticagrelor in healthy subjects. Eur J Clin Pharmacol. 2013;69:877–83.PubMed
81.
Storey RF, Husted S, Harrington RA, Heptinstall S, Wilcox RG, Peters G, et al. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes. J Am Coll Cardiol. 2007;50:1852–6.PubMed
82.
Van Giezen JJJ, Humphries RG. Preclinical and clinical studies with selective reversible direct P2Y12 antagonists. Semin Thromb Hemost. 2005;31:195–204.PubMed
83.
Husted S, Emanuelsson H, Heptinstall S, Sandset PM, Wickens M, Peters G. Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. Eur Heart J. 2006;27:1038–47.PubMed
84.
Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009;120:2577–85.PubMed
85.
Rollini F, Franchi F, Cho JR, Degroat C, Bhatti M, Muniz-Lozano A, et al. A head-to-head pharmacodynamic comparison of prasugrel vs. ticagrelor after switching from clopidogrel in patients with coronary artery disease: results of a prospective randomized study. Eur Heart J. 2016;37:2722–30.PubMed
86.
Akers WS, Oh JJ, Oestreich JH, Ferraris S, Wethington M, Steinhubl SR. Pharmacokinetics and pharmacodynamics of a bolus and infusion of cangrelor: a direct, parenteral P2Y12 receptor antagonist. J Clin Pharmacol. 2010;50:27–35.PubMed
87.
Franchi F, Rollini F, Muñiz-Lozano A, Rae Cho J, Angiolillo DJ. Cangrelor: a review on pharmacology and clinical trial development. Expert Rev Cardiovasc Ther. 2013;11:1279–91.PubMed
88.
Waite LH, Phan YL, Spinler SA. Cangrelor: a novel intravenous antiplatelet agent with a questionable future. Pharmacotherapy. 2014;34:1061–76.PubMed
89.
Ferri N, Corsini A, Bellosta S. Pharmacology of the new P2Y12 receptor inhibitors: insights on pharmacokinetic and pharmacodynamic properties. Drugs. 2013;73:1681–709.PubMed
90.
91.
Wagner H, Angiolillo DJ, ten Berg JM, Bergmeijer TO, Jakubowski JA, Small DS, et al. Higher body weight patients on clopidogrel maintenance therapy have lower active metabolite concentrations, lower levels of platelet inhibition, and higher rates of poor responders than low body weight patients. J Thromb Thromb. 2013;38:127–36.
92.
Angiolillo DJ, Fernández-Ortiz A, Bernardo E, Barrera Ramírez C, Sabaté M, Fernandez C, et al. Platelet aggregation according to body mass index in patients undergoing coronary stenting: should clopidogrel loading-dose be weight adjusted? J Invasive Cardiol. 2004;16:169–74.PubMed
93.
Small DS, Farid NA, Payne CD, Konkoy CS, Jakubowski JA, Winters KJ, et al. Effect of intrinsic and extrinsic factors on the clinical pharmacokinetics and pharmacodynamics of prasugrel. Clin Pharmacokinet. 2010;49:777–98.PubMed
94.
95.
Wrishko RE, Ernest CS 2nd, Small DS, Li YG, Weerakkody GJ, Riesmeyer JR, et al. Population pharmacokinetic analyses to evaluate the influence of intrinsic and extrinsic factors on exposure of prasugrel active metabolite in TRITON-TIMI 38. J Clin Pharmacol. 2009;49:984–98.PubMed
96.
97.
Price MJ, Murray SS, Angiolillo DJ, Lillie E, Smith EN, Tisch RL, et al. Influence of genetic polymorphisms on the effect of high- and standard-dose clopidogrel after percutaneous coronary intervention: the GIFT (Genotype Information and Functional Testing) study. J Am Coll Cardiol. 2012;59:1928–37.PubMed
98.
Berger JS, Bhatt DL, Cannon CP, Chen Z, Jiang L, Jones JB, et al. The relative efficacy and safety of clopidogrel in women and men: a sex-specific collaborative meta-analysis. J Am Coll Cardiol. 2009;54:1935–45.PubMed
99.
Teng R, Mitchell P, Butler K. Effect of age and gender on pharmacokinetics and pharmacodynamics of a single ticagrelor dose in healthy individuals. Eur J Clin Pharmacol. 2012;68:1175–82.PubMed
100.
Qamar A, Bhatt DL. Optimizing the use of cangrelor in the real world. Am J Cardiovasc Drugs. 2017;17:5–16.PubMed
101.
Lau ES, Braunwald E, Murphy SA, Wiviott SD, Bonaca MP, Husted S, et al. Potent P2Y12 inhibitors in men versus women: a collaborative meta-analysis of randomized trials. J Am Coll Cardiol. 2017;69:1549–59.PubMed
102.
Karazniewicz-Lada M, Danielak D, Burchardt P, Kruszyna L, Komosa A, Lesiak M, et al. Clinical pharmacokinetics of clopidogrel and its metabolites in patients with cardiovascular diseases. Clin Pharmacokinet. 2014;53:155–64.PubMed
103.
Small DS, Wrishko RE, Ernest CS, Ni L, Winters KJ, Farid NA, et al. Effect of age on the pharmacokinetics and pharmacodynamics of prasugrel during multiple dosing. Drugs Aging. 2009;26:781–90.PubMed
104.
Levine GN, Jeong YH, Goto S, Anderson JL, Huo Y, Mega JL, et al. Expert consensus document: World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI. Nat Rev Cardiol. 2014;11:597–606.PubMed
105.
Jiang XL, Samant S, Lesko LJ, Schmidt S. Clinical pharmacokinetics and pharmacodynamics of clopidogrel. Clin Pharmacokinet. 2015;54:147–66.PubMedPubMedCentral
106.
Martis S, Peter I, Hulot J-S, Kornreich R, Desnick RJ, Scott SA. Multi-ethnic distribution of clinically relevant CYP2C genotypes and haplotypes. Pharmacogenom J. 2013;13:369–77.
107.
Small DS, Payne CD, Kothare P, Yuen E, Natanegara F, Teng Loh M, et al. Pharmacodynamics and pharmacokinetics of single doses of prasugrel 30 mg and clopidogrel 300 mg in healthy Chinese and white volunteers: an open-label trial. Clin Ther. 2010;32:365–79.PubMed
108.
109.
Teng R, Butler K. Pharmacokinetics, pharmacodynamics, and tolerability of single and multiple doses of ticagrelor in Japanese and Caucasian volunteers. Int J Clin Pharmacol Ther. 2014;52:478–91.PubMed
110.
Gaglia MA, Lipinski MJ, Lhermusier T, Steinvil A, Kiramijyan S, Pokharel S, et al. Comparison of platelet reactivity in black versus white patients with acute coronary syndromes after treatment with ticagrelor. Am J Cardiol. 2017;119:1135–40.PubMed
111.
Price MJ, Clavijo L, Angiolillo DJ, Carlson G, Caplan R, Teng R, et al. A randomised trial of the pharmacodynamic and pharmacokinetic effects of ticagrelor compared with clopidogrel in hispanic patients with stable coronary artery disease. J Thromb Thromb. 2015;39:8–14.
112.
113.
Cacabelos R. The metabolomic paradigm of pharmacogenomics in complex disorders. J Postgenom Drug Biomark Dev. 2012;2:5–7.
114.
Ingelman-Sundberg M, Sim SC, Gomez A, Rodriguez-Antona C. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther. 2007;116:496–526.PubMed
115.
Hulot J-S, Bura A, Villard E, Azizi M, Remones V, Goyenvalle C, et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood. 2006;108:2244–7.PubMed
116.
Wang X, Shen C, Wang B, Huang X, Hu Z, Li J. Genetic polymorphisms of CYP2C19*2 and ABCB1 C3435T affect the pharmacokinetic and pharmacodynamic responses to clopidogrel in 401 patients with acute coronary syndrome. Gene. 2015;558:200–7.PubMed
117.
Zabalza M, Subirana I, Sala J, Lluis-Ganella C, Lucas G, Tomás M, et al. Meta-analyses of the association between cytochrome CYP2C19 loss- and gain-of-function polymorphisms and cardiovascular outcomes in patients with coronary artery disease treated with clopidogrel. Heart. 2012;98:100–8.PubMed
118.
Cavallari LH, Lee CR, Beitelshees AL, Cooper-DeHoff RM, Duarte JD, Voora D, et al. Multisite investigation of outcomes with implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention. JACC Cardiovasc Interv. 2018;11:181–91.PubMed
119.
Joo HJ, Ahn SG, Park JH, Park JY, Hong SJ, Kim SY, et al. Effects of genetic variants on platelet reactivity and 1-year clinical outcomes after percutaneous coronary intervention: a prospective multicentre registry study. Sci Rep. 2018;8:1–9.
120.
Park KW, Park JJ, Jeon KH, Kang SH, Oh IY, Yang HM, et al. Enhanced clopidogrel responsiveness in smokers: Smokers’ paradox is dependent on cytochrome P450 CYP1A2 status. Arterioscler Thromb Vasc Biol. 2011;31:665–71.PubMed
121.
Ghotbi R, Christensen M, Roh HK, Ingelman-Sundberg M, Aklillu E, Bertilsson L. Comparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype–phenotype relationship in Swedes and Koreans. Eur J Clin Pharmacol. 2007;63:537–46.PubMed
122.
Lewis JP, Horenstein RB, Ryan K, O’Connell JR, Gibson Q, Mitchell BD, et al. The functional G143E variant of carboxylesterase 1 is associated with increased clopidogrel active metabolite levels and greater clopidogrel response. Pharmacogenet Genom. 2013;23:1–8.
123.
Xiao FY, Luo JQ, Liu M, Chen BL, Cao S, Liu ZQ, et al. Effect of carboxylesterase 1 S75N on clopidogrel therapy among acute coronary syndrome patients. Sci Rep. 2017;7:1–6.
124.
Jaitner J, Morath T, Byrne RA, Braun S, Gebhard D, Bernlochner I, et al. No association of ABCB1 C3435T genotype with clopidogrel response or risk of stent thrombosis in patients undergoing coronary stenting. Circ Cardiovasc Interv. 2012;5(82–8):S1–2.
125.
Su J, Xu J, Li X, Zhang H, Hu J, Fang R, et al. ABCB1 C3435T polymorphism and response to clopidogrel treatment in coronary artery disease (CAD) patients: a meta-analysis. PLoS One. 2012;7:e46366.PubMedPubMedCentral
126.
Luo M, Li J, Xu X, Sun X, Sheng W. ABCB1 C3435T polymorphism and risk of adverse clinical events in clopidogrel treated patients: a meta-analysis. Thromb Res. 2012;129:754–9.PubMed
127.
Cui G, Zhang S, Zou J, Chen Y, Chen H. P2Y12 receptor gene polymorphism and the risk of resistance to clopidogrel: a meta-analysis and review of the literature. Adv Clin Exp Med. 2017;26:343–9.PubMed
128.
Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, et al. Cytochrome P450 genetic polymorphisms and the response to prasugrel relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation. 2009;119:2553–60.PubMed
129.
Holmberg MT, Tornio A, Paile-Hyvärinen M, Tarkiainen EK, Neuvonen M, Neuvonen PJ, et al. CYP3A4*22 impairs the elimination of ticagrelor, but has no significant effect on the bioactivation of clopidogrel or prasugrel. Clin Pharmacol Ther. 2019;105:448–57.PubMed
130.
Tantry US, Bliden KP, Wei C, Storey RF, Armstrong M, Butler K, et al. First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: the ONSET/OFFSET and RESPOND genotype studies. Circ Cardiovasc Genet. 2010;3:556–66.PubMed
131.
Wang H, Qi J, Li Y, Tang Y, Li C, Li J, et al. Pharmacodynamics and pharmacokinetics of ticagrelor vs. clopidogrel in patients with acute coronary syndromes and chronic kidney disease. Br J Clin Pharmacol. 2018;84:88–96.PubMed
132.
Deray G, Bagnis C, Brouard R, Necciari J, Leenhardt AF, Raymond F, et al. Clopidogrel activities in patients with renal function impairment. Clin Drug Investig. 1998;16:319–28.PubMed
133.
Small DS, Wrishko RE, Ernest CS, Ni L, Winters KJ, Farid NA, et al. Prasugrel pharmacokinetics and pharmacodynamics in subjects with moderate renal impairment and end-stage renal disease. J Clin Pharm Ther. 2009;34:585–94.PubMed
134.
Butler K, Teng R. Pharmacokinetics, pharmacodynamics, and safety of ticagrelor in volunteers with severe renal impairment. J Clin Pharmacol. 2012;52:1388–98.PubMed
135.
Small DS, Farid NA, Li YG, Ernest CS, Winters KJ, Salazar DE, et al. Pharmacokinetics and pharmacodynamics of prasugrel in subjects with moderate liver disease. J Clin Pharm Ther. 2009;34:575–83.PubMed
136.
Butler K, Teng R. Pharmacokinetics, pharmacodynamics, and safety of ticagrelor in volunteers with mild hepatic impairment. J Clin Pharmacol. 2011;51:978–87.PubMed
137.
Rollini F, Franchi F, Muñiz-Lozano A, Angiolillo DJ. Platelet function profiles in patients with diabetes mellitus. J Cardiovasc Transl Res. 2013;6:329–45.PubMed
138.
Sweeny JM, Angiolillo DJ, Franchi F, Rollini F, Waksman R, Raveendran G, et al. Impact of diabetes mellitus on the pharmacodynamic effects of ticagrelor versus clopidogrel in troponin-negative acute coronary syndrome patients undergoing ad hoc percutaneous coronary intervention. J Am Heart Assoc. 2017;6:1–10.
139.
Lee RH, Bergmeier W. Sugar makes neutrophils RAGE: linking diabetes-associated hyperglycemia to thrombocytosis and platelet reactivity. J Clin Investig. 2017;127:2040–3.PubMed
140.
Ferreiro JL, Angiolillo DJ. Diabetes and antiplatelet therapy in acute coronary syndrome. Circulation. 2011;123:798–813.PubMed
141.
Hu L, Chang L, Zhang Y, Zhai L, Zhang S, Qi Z, et al. Platelets express activated P2Y12 receptor in patients with diabetes mellitus. Circulation. 2017;136:817–33.PubMed
142.
Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Ramírez C, Sabaté M, Jimenez-Quevedo P, et al. Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment. Diabetes. 2005;54:2430–5.PubMed
143.
Angiolillo DJ, Jakubowski JA, Ferreiro JL, Tello-Montoliu A, Rollini F, Franchi F, et al. Impaired responsiveness to the platelet P2Y12 receptor antagonist clopidogrel in patients with type 2 diabetes and coronary artery disease. J Am Coll Cardiol. 2014;64:1005–14.PubMed
144.
Angiolillo DJ, Badimon JJ, Saucedo JF, Frelinger AL, Michelson AD, Jakubowski JA, et al. A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy in diabetes MellitUS (OPTIMUS)-3 Trial. Eur Heart J. 2011;32:838–46.PubMedPubMedCentral
145.
Franchi F, Rollini F, Aggarwal N, Hu J, Kureti M, Durairaj A, et al. Pharmacodynamic comparison of prasugrel versus ticagrelor in patients with type 2 diabetes mellitus and coronary artery disease: the OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 Study. Circulation. 2016;134:780–92.PubMed
146.
Franchi F, James SK, Ghukasyan Lakic T, Budaj AJ, Cornel JH, Katus HA, et al. Impact of diabetes mellitus and chronic kidney disease on cardiovascular outcomes and platelet P2Y12 receptor antagonist effects in patients with acute coronary syndromes: insights from the PLATO Trial. J Am Heart Assoc. 2019;8(6):e011139.PubMedPubMedCentral
147.
Alexopoulos D, Xanthopoulou I, Mavronasiou E, Stavrou K, Siapika A, Tsoni E, et al. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with diabetes. Diabetes Care. 2013;36:2211–6.PubMedPubMedCentral
148.
Ferreiro JL, Ueno M, Tello-Montoliu A, Tomasello SD, Capodanno D, Capranzano P, et al. Effects of cangrelor in coronary artery disease patients with and without diabetes mellitus: an in vitro pharmacodynamic investigation. J Thromb Thromb. 2013;35:155–64.
149.
Frelinger AL, Lee RD, Mulford DJ, Wu J, Nudurupati S, Nigam A, et al. A randomized, 2-period, crossover design study to assess the effects of dexlansoprazole, lansoprazole, esomeprazole, and omeprazole on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers. J Am Coll Cardiol. 2012;59:1304–11.PubMed
150.
Simon N, Finzi J, Cayla G, Montalescot G, Collet JP, Hulot JS. Omeprazole, pantoprazole, and CYP2C19 effects on clopidogrel pharmacokinetic–pharmacodynamic relationships in stable coronary artery disease patients. Eur J Clin Pharmacol. 2015;71:1059–66.PubMed
151.
Gilard M, Arnaud B, Cornily JC, Le Gal G, Lacut K, Le Calvez G, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) Study. J Am Coll Cardiol. 2008;51:256–60.PubMed
152.
Ferreiro JL, Ueno M, Capodanno D, Desai B, Dharmashankar K, Darlington A, et al. Pharmacodynamic effects of concomitant versus staggered clopidogrel and omeprazole intake. Circ Cardiovasc Interv. 2010;3:436–41.PubMed
153.
Farid NA, Payne CD, Small DS, Winters KJ, Ernest CS, Brandt JT, et al. Cytochrome P450 3A inhibition by ketoconazole affects prasugrel and clopidogrel pharmacokinetics and pharmacodynamics differently. Clin Pharmacol Ther. 2007;81:735–41.PubMed
154.
Lau WC, Waskell LA, Watkins PB, Neer CJ, Horowitz K, Hopp AS, et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug–drug interaction. Circulation. 2003;107:32–7.PubMed
155.
Judge HM, Patil SB, Buckland RJ, Jakubowski JA, Storey RF. Potentiation of clopidogrel active metabolite formation by rifampicin leads to greater P2Y12 receptor blockade and inhibition of platelet aggregation after clopidogrel. J Thromb Haemost. 2010;8:1820–7.PubMed
156.
Duarte GS, Nunes-Ferreira A, Rodrigues FB, Pinto FJ, Ferreira JJ, Costa J, et al. Morphine in acute coronary syndrome: systematic review and meta-analysis. BMJ Open. 2019;9:e025232.PubMedPubMedCentral
157.
Hobl EL, Stimpfl T, Ebner J, Schoergenhofer C, Derhaschnig U, Sunder-Plassmann R, et al. Morphine decreases clopidogrel concentrations and effects: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol. 2014;63:630–5.PubMed
158.
Zeymer U, Mark B, Montalescot G, Thiele H, Zahn R. Influence of morphine on the effect of clopidogrel and prasugrel in patients with ST elevation myocardial infarction: results of the ETAMI trial. Eur Heart J. 2015;36:227–8.
159.
Clarke T, Waskell L. The metabolism of clopidogrel is catalyzed by human cytochrome P450 3A and is inhibited by atorvastatin. Drug Metab Dispos. 2003;31:53–9.PubMed
160.
Farid NA, Small DS, Payne CD, Jakubowski JA, Brandt JT, Li YG, et al. Effect of atorvastatin on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in healthy subjects. Pharmacotherapy. 2008;28:1483–94.PubMed
161.
Kreutz RP, Breall JA, Sinha A, von der Lohe E, Kovacs RJ, Flockhart DA. Simultaneous administration of high-dose atorvastatin and clopidogrel does not interfere with platelet inhibition during percutaneous coronary intervention. Clin Pharmacol Adv Appl. 2016;8:45–50.
162.
Trenk D, Hochholzer W, Frundi D, Stratz C, Valina CM, Bestehorn H-P, et al. Impact of cytochrome P450 3A4-metabolized statins on the antiplatelet effect of a 600-mg loading dose clopidogrel and on clinical outcome in patients undergoing elective coronary stent placement. Thromb Haemost. 2008;99:174–81.PubMed
163.
Leoncini M, Toso A, Maioli M, Angiolillo DJ, Giusti B, Marcucci R, et al. High-dose atorvastatin on the pharmacodynamic effects of double-dose clopidogrel in patients undergoing percutaneous coronary interventions. JACC Cardiovasc Interv. 2013;6:169–79.PubMed
164.
Karaźniewicz-Łada M, Rzeźniczak J, Główka F, Gumienna A, Dolatowski F, Słomczyński M, et al. Influence of statin treatment on pharmacokinetics and pharmacodynamics of clopidogrel and its metabolites in patients after coronary angiography/angioplasty. Biomed Pharmacother. 2019;116:108991.PubMed
165.
Verdoia M, Nardin M, Sartori C, Pergolini P, Rolla R, Barbieri L, et al. Impact of atorvastatin or rosuvastatin co-administration on platelet reactivity in patients treated with dual antiplatelet therapy. Atherosclerosis. 2015;243:389–94.PubMed
166.
Suh J-W, Cha M-J, Lee S-P, Chae I-H, Bae J-H, Kwon T-G, et al. Relationship between statin type and responsiveness to clopidogrel in patients treated with percutaneous coronary intervention: a subgroup analysis of the CILON-T trial. J Atheroscler Thromb. 2014;21:140–50.PubMed
167.
Oh J, Shin D, Lim KS, Lee S, Jung KH, Chu K, et al. Aspirin decreases systemic exposure to clopidogrel through modulation of P-glycoprotein but does not alter its antithrombotic activity. Clin Pharmacol Ther. 2014;95:608–16.PubMed
168.
Liang Y, Hirsh J, Weitz JI, Sloane D, Gao P, Pare G, et al. Active metabolite concentration of clopidogrel in patients taking different doses of aspirin: results of the interaction trial. J Thromb Haemost. 2015;13:347–52.PubMed
169.
Gurbel PA, Bliden KP, Logan DK, Kereiakes DJ, Lasseter KC, White A, et al. The influence of smoking status on the pharmacokinetics and pharmacodynamics of clopidogrel and prasugrel: the paradox study. J Am Coll Cardiol. 2013;62:505–12.PubMed
170.
Swiger KJ, Yousuf O, Bliden KP, Tantry US, Gurbel PA. Cigarette smoking and clopidogrel interaction. Curr Cardiol Rep. 2013;15:21–9.
171.
Itkonen MK, Tornio A, Neuvonen M, Neuvonen PJ, Niemi M, Backman JT. Clopidogrel has no clinically meaningful effect on the pharmacokinetics of the OATP1B1 and CYP3A4 substrate simvastatin. Drug Metab Dispos. 2015;1655–60.
172.
Tornio A, Filppula AM, Kailari O, Neuvonen M, Nyrönen TH, Tapaninen T, et al. Glucuronidation converts clopidogrel to a strong time-dependent inhibitor of CYP2C8: a phase II metabolite as a perpetrator of drug–drug interactions. Clin Pharmacol Ther. 2014;96:498–507.PubMed
173.
174.
Ancrenaz V, Déglon J, Samer C, Staub C, Dayer P, Daali Y, et al. Pharmacokinetic interaction between prasugrel and ritonavir in healthy volunteers. Basic Clin Pharmacol Toxicol. 2013;112:132–7.PubMed
175.
Farid NA, Jakubowski JA, Payne CD, Li YG, Jin Y, Ernest CS II, et al. Effect of rifampin on the pharmacokinetics and pharmacodynamics of prasugrel in healthy male subjects. Curr Med Res Opin. 2009;25:1821–9.PubMed
176.
Small DS, Farid NA, Payne CD, Weerakkody GJ, Li YG, Brandt JT, et al. Effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel. J Clin Pharmacol. 2008;48:475–84.PubMed
177.
Hobl E-L, Reiter B, Schoergenhofer C, Schwameis M, Derhaschnig U, Lang IM, et al. Morphine interaction with prasugrel: a double-blind, cross-over trial in healthy volunteers. Clin Res Cardiol. 2016;105:349–55.PubMed
178.
Parodi G, Bellandi B, Xanthopoulou I, Capranzano P, Capodanno D, Valenti R, et al. Morphine is associated with a delayed activity of oral antiplatelet agents in patients with ST-elevation acute myocardial infarction undergoing primary percutaneous coronary intervention. Circ Cardiovasc Interv. 2015;8:1–6.
179.
Thomas MR, Morton AC, Hossain R, Chen B, Luo L, Shahari NNBM, et al. Morphine delays the onset of action of prasugrel in patients with prior history of ST-elevation myocardial infarction. Thromb Haemost. 2016;116:96–102.PubMed
180.
Johnson TW, Mumford AD, Scott LJ, Mundell S, Butler M, Strange JW, et al. A study of platelet inhibition, using a “point of care” platelet function test, following primary percutaneous coronary intervention for ST-elevation myocardial infarction [PINPOINT-PPCI]. PLoS One. 2015;10:e0144984.PubMedPubMedCentral
181.
Teng R, Butler K. Effect of the CYP3A inhibitors, diltiazem and ketoconazole, on ticagrelor pharmacokinetics in healthy volunteers. J Drug Assess. 2013;2:30–9.PubMedPubMedCentral
182.
Teng R, Kujacic M, Hsia J. Pharmacokinetic interaction study of ticagrelor and cyclosporine in healthy volunteers. Clin Drug Investig. 2014;34:529–36.PubMed
183.
Hobl E-L, Reiter B, Schoergenhofer C, Schwameis M, Derhaschnig U, Kubica J, et al. Morphine decreases ticagrelor concentrations but not its antiplatelet effects: a randomized trial in healthy volunteers. Eur J Clin Investig. 2016;46:7–14.
184.
Kubica J, Adamski P, Ostrowska M, Sikora J, Kubica JM, Sroka WD, et al. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial. Eur Heart J. 2016;37:245–52.PubMed
185.
Silvain J, Storey RF, Cayla G, Esteve J-B, Dillinger J-G, Rousseau H, et al. P2Y12 receptor inhibition and effect of morphine in patients undergoing primary PCI for ST-segment elevation myocardial infarction: the PRIVATE-ATLANTIC study. Thromb Haemost. 2016;116:369–78.PubMed
186.
Kickler T, Thiemann D, Ibrahim K, Blumenthal R, Goli R, Hasan R, et al. Fentanyl delays the platelet inhibition effects of oral ticagrelor: full report of the PACIFY randomized clinical trial. Thromb Haemost. 2018;118:1409–18.PubMedPubMedCentral
187.
Teng R, Maya J, Butler K. Evaluation of the pharmacokinetics and pharmacodynamics of ticagrelor co-administered with aspirin in healthy volunteers. Platelets. 2013;24:615–24.PubMed
188.
Thomas MR, Storey RF. Impact of aspirin dosing on the effects of P2Y12 inhibition in patients with acute coronary syndromes. J Cardiovasc Transl Res. 2014;7:19–28.PubMed
189.
DiNicolantonio JJ, Serebruany VL. Challenging the FDA black box warning for high aspirin dose with ticagrelor in patients with diabetes. Diabetes. 2013;62:669–71.PubMedPubMedCentral
190.
Teng R, Butler K. The effect of ticagrelor on the metabolism of midazolam in healthy volunteers. Clin Ther. 2013;35:1025–37.PubMed
191.
Teng R, Butler K. A pharmacokinetic interaction study of ticagrelor and digoxin in healthy volunteers. Eur J Clin Pharmacol. 2013;69:1801–8.PubMed
192.
Teng R, Mitchell PD, Butler KA. Pharmacokinetic interaction studies of co-administration of ticagrelor and atorvastatin or simvastatin in healthy volunteers. Eur J Clin Pharmacol. 2013;69:477–87.PubMed
193.
Danielak D, Karaźniewicz-Łada M, Główka F. Ticagrelor in modern cardiology: an up-to-date review of most important aspects of ticagrelor pharmacotherapy. Expert Opin Pharmacother. 2018;19:103–12.PubMed
194.
Danielak D, Karaźniewicz-Łada M, Główka F. Assessment of the risk of rhabdomyolysis and myopathy during concomitant treatment with ticagrelor and statins. Drugs. 2018;78:1105–12.PubMedPubMedCentral
195.
Schneider DJ, Seecheran N, Raza SS, Keating FK, Gogo P. Pharmacodynamic effects during the transition between cangrelor and prasugrel. Coron Artery Dis. 2015;26:42–8.PubMed
196.
Schneider DJ, Agarwal Z, Seecheran N, Keating FK, Gogo P. Pharmacodynamic effects during the transition between cangrelor and ticagrelor. JACC Cardiovasc Interv. 2014;7:435–42.PubMed
197.
Schneider DJ, Agarwal Z, Seecheran N, Gogo P. Pharmacodynamic effects when clopidogrel is given before cangrelor discontinuation. J Interv Cardiol. 2015;28:415–9.PubMed
198.
Judge HM, Buckland RJ, Jakubowski JA, Storey RF. Cangrelor inhibits the binding of the active metabolites of clopidogrel and prasugrel to P2Y 12 receptors in vitro. Platelets. 2016;27:191–5.PubMed
199.
Savonitto S, De Luca G, Goldstein P, van t’ Hof A, Zeymer U, Morici N, et al. Antithrombotic therapy before, during and after emergency angioplasty for ST elevation myocardial infarction. Eur Hear J Acute Cardiovasc Care. 2017;6:173–90.
200.
Scott IA. “Time is muscle” in reperfusing occluded coronary arteries in acute myocardial infarction. Med J Aust. 2010;193:493–5.PubMed
201.
Makam RP, Erskine N, Yarzebski J, Lessard D, Lau J, Allison J, et al. Decade long trends (2001–2011) in duration of pre-hospital delay among elderly patients hospitalized for an acute myocardial infarction. J Am Heart Assoc. 2016;5:75–84.
202.
Saczynski JS, Yarzebski J, Lessard D, Spencer FA, Gurwitz JH, Gore JM, et al. Trends in prehospital delay in patients with acute myocardial infarction (from the Worcester Heart Attack Study). Am J Cardiol. 2008;102:1589–94.PubMedPubMedCentral
203.
Adamski P, Sikora J, Laskowska E, Buszko K, Ostrowska M, Uminska JM, et al. Comparison of bioavailability and antiplatelet action of ticagrelor in patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction: a prospective, observational, single-centre study. PLoS One. 2017;12:e0186013.PubMedPubMedCentral
204.
Wohner N. Role of cellular elements in thrombus formation and dissolution. Cardiovasc Hematol Agents Med Chem. 2008;6:224–8.PubMedPubMedCentral
205.
206.
Siller-Matula JM, Trenk D, Schrör K, Gawaz M, Kristensen SD, Storey RF, et al. Response variability to P2Y12receptor inhibitors: expectations and reality. JACC Cardiovasc Interv. 2013;6:1111–28.PubMed
207.
Jiang J, Chen X, Zhong D. Arylacetamide deacetylase is involved in vicagrel bioactivation in humans. Front Pharmacol. 2017;8:1–8.
208.
Liu C, Zhang Y, Chen W, Lu Y, Li W, Liu Y, et al. Pharmacokinetics and pharmacokinetic/pharmacodynamic relationship of vicagrel, a novel thienopyridine P2Y12 inhibitor, compared with clopidogrel in healthy Chinese subjects following single oral dosing. Eur J Pharm Sci. 2019;127:151–60.PubMed
209.
Shan J, Zhang B, Zhu Y, Jiao B, Zheng W, Qi X, et al. Overcoming clopidogrel resistance: discovery of vicagrel as a highly potent and orally bioavailable antiplatelet agent. J Med Chem. 2012;55:3342–52.PubMed
210.
Qiu Z, Li N, Song L, Lu Y, Jing J, Parekha HS, et al. Contributions of intestine and plasma to the presystemic bioconversion of vicagrel, an acetate of clopidogrel. Pharm Res. 2014;31:238–51.PubMed
211.
Li X, Liu C, Zhu X, Wei H, Zhang H, Chen H, et al. Evaluation of tolerability, pharmacokinetics and pharmacodynamics of vicagrel, a novel P2Y12 antagonist, in healthy chinese volunteers. Front Pharmacol. 2018;9:643.PubMedPubMedCentral
212.
Caroff E, Hubler F, Meyer E, Renneberg D, Gnerre C, Treiber A, et al. 4-((R)-2-{[6-((S)-3-Methoxypyrrolidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino}-3-phosphonopropionyl)piperazine-1-carboxylic acid butyl ester (ACT-246475) and its prodrug (ACT-281959), a novel P2Y 12 receptor antagonist with a wider therapeutic window. J Med Chem. 2015;58:9133–53.PubMed
213.
Juif P-E, Boehler M, Dobrow M, Ufer M, Dingemanse J. Clinical pharmacology of the reversible and potent P2Y12 receptor antagonist ACT-246475 after single subcutaneous administration in healthy male subjects. J Clin Pharmacol. 2019;59:123–30.PubMed
214.
Ufer M, Huynh C, van Lier JJ, Caroff E, Fischer H, Dingemanse J. Absorption, distribution, metabolism and excretion of the P2Y12 receptor antagonist selatogrel after subcutaneous administration in healthy subjects. Xenobiotica. 2019;1–8.
215.
Schilling U, Ufer M, Dingemanse J. Effect of rifampin-mediated inhibition of the hepatic uptake transporters OATP1B1 and OATP1B3 on the pharmacokinetics of the P2Y12 receptor antagonist selatogrel (ACT-246475). Clin Pharmacol Drug Dev. 2019;8:22.
216.
Storey RF, Gurbel PA, ten Berg J, Bernaud C, Dangas GD, Frenoux J, et al. Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes. Eur Heart J. 2019;1–9.
217.
Siller-Matula JM, Trenk D, Krähenbühl S, Michelson AD, Delle-Karth G. Clinical implications of drug-drug interactions with P2Y12 receptor inhibitors. J Thromb Haemost. 2014;12:2–13.PubMed
Metadaten
Titel
Pharmacokinetics and Pharmacodynamics of Approved and Investigational P2Y12 Receptor Antagonists
verfasst von
Uta Schilling
Jasper Dingemanse
Mike Ufer
Publikationsdatum
13.02.2020
Verlag
Springer International Publishing
Erschienen in
Clinical Pharmacokinetics / Ausgabe 5/2020
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-020-00864-4

Weitere Artikel der Ausgabe 5/2020

Clinical Pharmacokinetics 5/2020 Zur Ausgabe

Original Research Article

Quantitative Assessment of Elagolix Enzyme-Transporter Interplay and Drug–Drug Interactions Using Physiologically Based Pharmacokinetic Modeling

Review Article

Clinical Pharmacokinetics and Pharmacodynamics of Imipenem–Cilastatin/Relebactam Combination Therapy

Original Research Article

Favorable Pharmacokinetic Characteristics of Extended-Half-Life Recombinant Factor VIII BAY 94-9027 Enable Robust Individual Profiling Using a Population Pharmacokinetic Approach

Original Research Article

Fetal Physiologically Based Pharmacokinetic Models: Systems Information on Fetal Blood Components and Binding Proteins

Letter to the Editor

Comment on “Levothyrox® New and Old Formulations: Are They Switchable for Millions of Patients?”

Original Research Article

Midazolam Pharmacokinetics in Obese and Non-obese Children and Adolescents