Pharmacokinetics, pharmacodynamics, and tolerability of single and multiple doses of ticagrelor in Japanese and Caucasian volunteers

International Journal of Clinical Pharmacology and Therapeutics

Volumn 52, Issue 6, 2014, Pages 478-491

  Teng, Renli ^a   Butler, Kathleen ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

Japanese; Pharmacodynamics; Pharmacokinetics; Ticagrelor

Indexed keywords

AR C124910XX; DRUG METABOLITE; PLACEBO; TICAGRELOR; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; BLEEDING TIME; BLOOD SAMPLING; CAUCASIAN; CONJUNCTIVITIS; CONTACT DERMATITIS; CONTROLLED STUDY; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPNEA; DYSURIA; ECCHYMOSIS; FAINTNESS; FEMALE; GINGIVA BLEEDING; HEADACHE; HEMATURIA; HUMAN; HUMAN EXPERIMENT; INJECTION SITE CONTUSION; JAPANESE (PEOPLE); MALE; MOOD DISORDER; MULTIPLE ASCENDING DOSE; NAUSEA; NEPHROLITHIASIS; NORMAL HUMAN; PHARMACODYNAMICS; PHARMACOLOGICAL PARAMETERS; PLASMA CONCENTRATION-TIME CURVE; POSITIONAL DIZZINESS; RANDOMIZED CONTROLLED TRIAL; SINGLE ASCENDING DOSE; SINGLE DRUG DOSE; TENSION HEADACHE; THROMBOCYTE AGGREGATION INHIBITION; TONSILLITIS; UNSPECIFIED SIDE EFFECT; XEROSTOMIA;

ADENOSINE; ADULT; AREA UNDER CURVE; ASIAN CONTINENTAL ANCESTRY GROUP; BIOTRANSFORMATION; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; HALF-LIFE; HEMORRHAGE; HUMANS; JAPAN; MALE; METABOLIC CLEARANCE RATE; PLATELET AGGREGATION; PLATELET AGGREGATION INHIBITORS; PLATELET FUNCTION TESTS; PURINERGIC P2Y RECEPTOR ANTAGONISTS; UNITED STATES; YOUNG ADULT;

EID: 84902135631     PISSN: 09461965     EISSN: None     Source Type: Journal    
DOI: 10.5414/CP202017     Document Type: Article

References (20)

1. 12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. Eur Heart J. 2006; 27: 1038-1047. CrossRef PubMed
2. 12 independently from ADP but antagonizes ADP-induced receptor signaling and platelet aggregation. J Thromb Haemost. 2009; 7: 1556-1565. CrossRef PubMed
3. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA, Freij A, Thorsén M; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009; 361: 1045-1057. CrossRef PubMed
4. Teng R, Butler K. AZD6140, the first reversible oral platelet P2Y12 receptor antagonist, has linear pharmacokinetics and provides near complete inhibition of platelet aggregation, with reversibility of effect, in healthy subjects. Can J Clin Pharmacol. 2008; 15: e426.
5. Butler K, Teng R. Pharmacokinetics, pharmacodynamics, safety and tolerability of multiple ascending doses of ticagrelor in healthy volunteers. Br J Clin Pharmacol. 2010; 70: 65-77. CrossRef PubMed
6. Teng R, Butler K. Pharmacokinetics, pharmacodynamics, tolerability and safety of single ascending doses of ticagrelor, a reversibly binding oral P2Y(12) receptor antagonist, in healthy subjects. Eur J Clin Pharmacol. 2010; 66: 487-496. CrossRef PubMed
7. Teng R, Oliver S, Hayes MA, Butler K. Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos. 2010; 38: 1514-1521. CrossRef PubMed
8. Zhou D, Andersson TB, Grimm SW. In vitro evaluation of potential drug-drug interactions with ticagrelor: cytochrome P450 reaction phenotyping, inhibition, induction, and differential kinetics. Drug Metab Dispos. 2011; 39: 703-710. CrossRef PubMed
9. Goto S, Toda E. Antiplatelet therapy after coronary intervention in Asia and Japan: the Asian perspective of antiplatelet intervention. Hämostaseologie. 2009; 29: 321-325. PubMed
10. Solus JF, Arietta BJ, Harris JR, Sexton DP, Steward JQ, McMunn C, Ihrie P, Mehall JM, Edwards TL, Dawson EP. Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics. 2004; 5: 895-931. CrossRef PubMed (Pubitemid 39386756)
11. Li H, Butler K, Yang L, Yang Z, Teng R. Pharmacokinetics and tolerability of single and multipledoses of ticagrelor in healthy Chinese subjects: an open-label, sequential, two-cohort, single-centre study. Clin Drug Investig. 2012; 32: 87-97. CrossRef PubMed
12. European Agency for the Evaluation of Medicinal Products, International Conference on Harmonisation-World Health Organization. Guideline for Good Clinical Practice. (EMEA Website). ICH Topic E6. Geneva, Switzerland: WHO. 2002; Available at: http://www.ema.europa.eu/docs/en-GB/document-library/Scientific- guideline/2009/09/WC500002874.pdf. Accessed February 2, 2012.
13. World Medical Association Declaration of Helsinki. Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Volunteers. (WMA Website). Ferney-Vottaire, France: WMA. 2008; Available at: http://www.wma.net/ en/30publications/10policies/b3/index.html. Accessed February 2, 2012.
14. Sillén H, Cook M, Davis P. Determination of ticagrelor and two metabolites in plasma samples by liquid chromatography and mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2010; 878: 2299-2306. CrossRef PubMed
15. Labarthe B, Théroux P, Angioï M, Ghitescu M. Matching the evaluation of the clinical efficacy of clopidogrel to platelet function tests relevant to the biological properties of the drug. J Am Coll Cardiol. 2005; 46: 638-645. CrossRef PubMed (Pubitemid 41132690)
16. van Riemsdijk MM, Sturkenboom MC, Ditters JM, Tulen JH, Ligthelm RJ, Overbosch D, Stricker BH. Low body mass index is associated with an increased risk of neuropsychiatric adverse events and concentration impairment in women on mefloquine. Br J Clin Pharmacol. 2004; 57: 506-512. CrossRef PubMed (Pubitemid 38519657)
17. Evans WE, McLeod HL. Pharmacogenomics - drug disposition, drug targets, and side effects. N Engl J Med. 2003; 348: 538-549. CrossRef PubMed (Pubitemid 36159890)
18. Weinshilboum R. Inheritance and drug response. N Engl J Med. 2003; 348: 529-537. CrossRef PubMed (Pubitemid 36159889)
19. Butler K, Teng R. Pharmacokinetics, pharmacodynamics, and safety of ticagrelor in volunteers with mild hepatic impairment. J Clin Pharmacol. 2011; 51: 978-987. CrossRef PubMed
20. Peterson P, Hayes TE, Arkin CF, Bovill EG, Fairweather RB, Rock WA Jr, Triplett DA, Brandt JT. The preoperative bleeding time test lacks clinical benefit: College of American Pathologists' and American Society of Clinical Pathologists' position article. Arch Surg. 1998; 133: 134-139. CrossRef PubMed (Pubitemid 28092910)