Pharmacokinetics, pharmacodynamics, and safety of ticagrelor in volunteers with mild hepatic impairment

Journal of Clinical Pharmacology

Volumn 51, Issue 7, 2011, Pages 978-987

  Butler, Kathleen ^a   Teng, Renli ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

antiplatelet therapy; mild hepatic impairment; pharmacodynamics; pharmacokinetics; Ticagrelor

Indexed keywords

AR C 124910XX; DRUG METABOLITE; PLASMA PROTEIN; TICAGRELOR; UNCLASSIFIED DRUG;

ABSENCE OF SIDE EFFECTS; ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; BLOOD ANALYSIS; CLINICAL ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DISEASE SEVERITY; DRUG BLOOD LEVEL; DRUG EXPOSURE; DRUG HALF LIFE; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG TOLERABILITY; ELECTROCARDIOGRAM; FEMALE; HUMAN; INDUCED PLATELET AGGREGATION; LIVER DYSFUNCTION; MALE; MAXIMUM PLASMA CONCENTRATION; OPEN STUDY; PARALLEL DESIGN; SIDE EFFECT; SINGLE DRUG DOSE; THROMBOCYTE AGGREGATION; TIME TO MAXIMUM PLASMA CONCENTRATION; VITAL SIGN;

ADENOSINE; ADULT; AGED; BIOTRANSFORMATION; FEMALE; HALF-LIFE; HEPATIC INSUFFICIENCY; HUMANS; MALE; MIDDLE AGED; PLATELET AGGREGATION; PLATELET AGGREGATION INHIBITORS; PURINERGIC P2Y RECEPTOR ANTAGONISTS; RECEPTORS, PURINERGIC P2Y12; SEVERITY OF ILLNESS INDEX;

EID: 79958782519     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270010379409     Document Type: Article

References (26)

1. Bassand JP, Hamm CW, Ardissino D, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J. 2007 ; 28: 1598-1660
2. Husted S, van Giezen JJ. Ticagrelor: the first reversibly binding oral P2Y receptor antagonist. Cardiovasc Ther. 2009 ; 27: 259-274
3. Husted S, Emanuelsson H, Heptinstall S, et al. 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: 1038-1047
4. Cannon CP, Husted S, Harrington RA, et al. Safety, tolerability, and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment elevation acute coronary syndrome: primary results of the DISPERSE-2 trial. J Am Coll Cardiol. 2007 ; 50: 1844-1851 (Pubitemid 350007959)
5. Storey RF, Husted S, Harrington RA, 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: 1852-1856 (Pubitemid 350017792)
6. James S, Akerblom A, Cannon CP, et al. Comparison of ticagrelor, the first reversible oral P2Y(12) receptor antagonist, with clopidogrel in patients with acute coronary syndromes: rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J. 2009 ; 157: 599-605
7. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 ; 361: 1045-57
8. 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
9. Butler K, Teng R. Pharmacokinetics, pharmacodynamics and safety and tolerability of multiple ascending doses of ticagrelor in healthy volunteers. Br J Clin Pharmacol. :
10. Teng R, Oliver S, Hayes M, Butler K. Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos. :
11. Tantry US, Bliden KP, Gurbel PA. Expert Opin Invest Drugs. 2007 ; 16: 225-229
12. Palatini P, De Martin S, Pegoraro P, Orlando R. Enzyme inhibition and induction in liver disease. Curr Clin Pharmacol. 2008 ; 3: 56-59
13. Verbeeck RK. Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction. Eur J Clin Pharmacol. 2008 ; 64: 1147-1161
14. Mackichan JJ, In Burton ME, Shaw LM, Schentag J, Evans WE Applied Pharmacokinetics and Pharmacodynamics: Principles of Therapeutic Drug Monitoring. Baltimore, Md: Lippincott Williams & Wilkins ; 2006: 82-120.
15. Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev. 2009 ; 41: 67-76
16. Møller S, Dümcke CW, Kragg A. The heart and the liver. Expert Rev Gastroenterol Hepatol. 2009 ; 3: 51-64
17. Fujimoto K, Sawabe M, Sasaki M, et al. Undiagnosed cirrhosis occurs frequently in the elderly and requires periodic follow ups and medical treatments. Geriatr Gerontol Int. 2008 ; 8: 198-203
18. US FDA, Guidance for Industry-pharmacokinetics in patients with impaired hepatic function: study design, data analysis, and impact on dosing and labeling. http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/ucm072123.pdf. Accessed October 15, 2009.
19. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973 ; 60: 646-649
20. Albers I, Hartmann H, Bircher J, Creutzfeldt W. Superiority of the Child-Pugh classification to quantitative liver function tests for assessing prognosis of liver cirrhosis. Scand J Gastroenterol. 1989 ; 24: 269-276 (Pubitemid 19110881)
21. Sillén H, Cook M, Davis P. Determination of ticagrelor and two metabolites in plasma samples by liquid chromatography and mass spectrometry. J Chromatogr B. :
22. European Medicines Agency, Committee for Medicinal products for Human use. Guideline on the evaluation of the pharmacokinetics of medicinal products in patients with impaired hepatic function (2005). http://www.emea.europa.eu/ pdfs/human/ewp/233902en. Accessed October 16, 2009.
23. Morgan DJ, McLean AJ. Clinical pharmacokinetic and pharmacodynamic considerations in patients with liver disease: an update. Clin Pharmacokinet. 1995 ; 29: 370-391
24. Butler K, Mitchell P, Teng R. Effect of age and gender on the pharmacokinetics and pharmacodynamics of a single ticagrelor dose in healthy subjects. Clin Pharmacol Ther. 2009 ; 85: S9-36
25. 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: 487-496
26. Verbeeck RK, Horsmans Y. Effect of hepatic insufficiency on pharmacokinetics and drug dosing. Pharm World Sci. 1998 ; 20: 183-192 (Pubitemid 28500179)