Prasugrel in children with sickle cell disease: Pharmacokinetic and pharmacodynamic data from an open-label, adaptive-design, dose-ranging study

Journal of Pediatric Hematology/Oncology

Volumn 37, Issue 1, 2015, Pages 1-9

  Styles, Lori ^a   Heiselman, Darell ^b   Heath, Lori E ^b   Moser, Brian A ^b   Small, David S ^b   Jakubowski, Joseph A ^b   Zhou, Chunmei ^b   Redding Lallinger, Rupa ^c   Heeney, Matthew M ^d   Quinn, Charles T ^e   Rana, Sohail R ^f   Kanter, Julie ^g   Winters, Kenneth J ^b  

^a CHILDREN S HOSPITAL OAKLAND RESEARCH INSTITUTE   (United States)

^b ELI LILLY AND COMPANY   (United States)

^c UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^d BOSTON CHILDREN S HOSPITAL   (United States)

^e CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

^f HOWARD UNIVERSITY   (United States)

^g MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

pediatric patients; pharmacodynamics; pharmacokinetics; prasugrel; safety; sickle cell disease

Indexed keywords

PRASUGREL; ANTITHROMBOCYTIC AGENT; PIPERAZINE DERIVATIVE; PURINERGIC P2Y RECEPTOR ANTAGONIST; THIOPHENE DERIVATIVE;

ADOLESCENT; AREA UNDER THE CURVE; ARTICLE; BLEEDING; CHILD; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG SAFETY; DRUG TOLERABILITY; EPISTAXIS; FEMALE; HUMAN; MALE; MULTICENTER STUDY; PHASE 2 CLINICAL TRIAL; PLATELET REACTIVITY; SICKLE CELL ANEMIA; ANEMIA, SICKLE CELL; BIOLOGICAL MODEL; BLOOD; CLINICAL TRIAL; METHODOLOGY; PRESCHOOL CHILD;

ADOLESCENT; ANEMIA, SICKLE CELL; CHILD; CHILD, PRESCHOOL; FEMALE; HUMANS; MALE; MODELS, BIOLOGICAL; PIPERAZINES; PLATELET AGGREGATION INHIBITORS; PURINERGIC P2Y RECEPTOR ANTAGONISTS; RESEARCH DESIGN; THIOPHENES;

EID: 84920563465     PISSN: 10774114     EISSN: 15363678     Source Type: Journal    
DOI: 10.1097/MPH.0000000000000291     Document Type: Article

References (30)

1. Genes and human disease. Available at: http://www.who.int/genomics/public/geneticdiseases/en/index2.html. Accessed September 10, 2013.
2. Sickle cell disease is a global public health issue. Available at: http://www.sicklecelldisease.org/index.cfm?page=scd-global. Accessed September 10, 2013.
3. Steinberg MH. Management of sickle cell disease. N Engl J Med. 1999;340:1021-1030.
4. Osarogiagbon UR, Choong S, Belcher JD, et al. Reperfusion injury pathophysiology in sickle transgenic mice. Blood. 2000; 96:314-320.
5. Kato GJ, Hebbel RP, Steinberg MH, et al. Vasculopathy in sickle cell disease: biology, pathophysiology, genetics, transla-tional medicine, and new research directions. Am J Hematol. 2009;84:618-625.
6. Serjeant GR. Sickle-cell disease. Lancet. 1997;350:725-730.
7. Wun T, Paglieroni T, Tablin F, et al. Platelet activation and platelet-erythrocyte aggregates in patients with sickle cell anemia. J Lab Clin Med. 1997;129:507-516.
8. Beurling-Harbury C, Schade SG. Platelet activation during pain crisis in sickle cell anemia patients. Am J Hematol. 1989; 31:237-241.
9. Jakubowski JA, Winters KJ, Naganuma H, et al. Prasugrel: a novel thienopyridine antiplatelet agent: a review of preclinical and clinical studies and the mechanistic basis for its distinct antiplatelet profile. Cardiovasc Drug Rev. 2007;25:357-374.
10. Cabannes R, Lonsdorfer J, Castaigne JP, et al. Clinical and biological double-blind-study of ticlopidine in preventive treatment of sickle-cell disease crises. Agents Actions Suppl. 1984;15:199-212.
11. Greenberg J, Ohene-Frempong K, Halus J, et al. Trial of low doses of aspirin as prophylaxis in sickle cell disease. J Pediatr. 1983;102:781-784.
12. Lee SP, Ataga KI, Zayed M, et al. Phase I study of eptifibatide in patients with sickle cell anaemia. Br J Haematol. 2007;139:612-620.
13. Osamo NO, Photiades DP, Famodu AA. Therapeutic effect of aspirin in sickle cell anaemia. Acta Haematol. 1981;66: 102-107.
14. Semple MJ, Al-Hasani SF, Kioy P, et al. A double-blind trial of ticlopidine in sickle cell disease. Thromb Haemost. 1984;51:303-306.
15. Zago MA, Costa FF, Ismael SJ, et al. Treatment of sickle cell diseases with aspirin. Acta Haematol. 1984;72:61-64.
16. Niitsu Y, Jakubowski JA, Sugidachi A, et al. Pharmacology of Cs-747 (prasugrel, LY640315), a novel, potent antiplatelet agent with in vivo P2Y#inf#12#/inf# receptor antagonist activity. Semin Thromb Hemost. 2005;31:184-194.
17. Jakubowski JA, Matsushima N, Asai F, et al. A multiple dose study of prasugrel (Cs-747), a novel thienopyridine P2Y#inf#12#/inf# inhibitor, compared with clopidogrel in healthy humans. Br J Clin Pharmacol. 2007;63:421-430.
18. Jakubowski JA, Payne CD, Brandt JT, et al. The platelet inhibitory effects and pharmacokinetics of prasugrel after administration of loading and maintenance doses in healthy subjects. J Cardiovasc Pharmacol. 2006;47:377-384.
19. Small DS, Farid NA, Payne CD, et al. Effect of intrinsic and extrinsic factors on the clinical pharmacokinetics and pharma-codynamics of prasugrel. Clin Pharmacokinet. 2010;49: 777-798.
20. Jakubowski JA, Zhou C, Small DS, et al. A phase 1 study of prasugrel in patients with sickle cell disease: pharmacokinetics and effects on ex vivo platelet reactivity. Br J Clin Pharmacol. 2013;75:1433-1444.
21. Jakubowski JA, Zhou C, Jurcevic S, et al. A phase 1 study of prasugrel in patients with sickle cell disease: effects on biomarkers of platelet activation and coagulation. Thromb Res. 2014;133:190-195.
22. Wun T, Soulieres D, Frelinger AL, et al. A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease. J Hematol Oncol. 2013;6:17.
23. Ernest CS II, Small DS, Rohatagi S, 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.
24. Jakubowski JA, Payne CD, Li YG, et al. The use of the VerifyNow P2Y12 point-of-care device to monitor platelet function across a range of P2Y#inf#12#/inf# inhibition levels following prasugrel and clopidogrel administration. Thromb Haemost. 2008;99:409-415.
25. Farid NA, McIntosh M, Garofolo F, et al. Determination of the active and inactive metabolites of prasugrel in human plasma by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2007;21:169-179.
26. Jakubowski JA, Payne CD, Li YG, et al. A comparison of the antiplatelet effects of prasugrel and high-dose clopidogrel as assessed by VASP-phosphorylation and light transmission aggregometry. Thromb Haemost. 2008;99: 215-222.
27. Jakubowski JA, Payne CD, Weerakkody GJ, et al. Dose-dependent inhibition of human platelet aggregation by prasugrel and its interaction with aspirin in healthy subjects. J Cardiovasc Pharmacol. 2007;49:167-173.
28. Li JS, Yow E, Berezny KY, et al. Dosing of clopidogrel for platelet inhibition in infants and young children: primary results of the platelet inhibition in children on clopidogrel (PICOLO) trial. Circulation. 2008;117:553-559.
29. Wessel DL, Berger F, Li JS, et al. Abstract 19459: a randomized trial of clopidogrel to reduce mortality and shunt-related morbidity in infants palliated with a systemic to pulmonary artery shunt. Circulation. 2010;122:A19459.
30. Thebault JJ, Kieffer G, Lowe GD, et al. Repeated-dose pharmacodynamics of clopidogrel in healthy subjects. Semin Thromb Hemost. 1999;25(suppl 2):9-14.