Evaluation of the pharmacokinetic interaction between ticagrelor and tolbutamide, a cytochrome P450 2C9 substrate, in healthy volunteers

International Journal of Clinical Pharmacology and Therapeutics

Volumn 51, Issue 4, 2013, Pages 305-312

  Teng, Renli ^a   Mitchell, Patrick ^a   Butler, Kathleen ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

CYP2C9; Drug drug interaction; Pharma cokinetics; Ticagrelor; Tolbutamide

Indexed keywords

CYTOCHROME P450 2C9; PLACEBO; TICAGRELOR; TOLBUTAMIDE;

ADULT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIZZINESS; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG ELIMINATION; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG METABOLISM; DRUG POTENTIATION; DRUG SAFETY; DRUG SCREENING; DRUG TOLERABILITY; DRUG WITHDRAWAL; DRY SKIN; FEMALE; HUMAN; HUMAN EXPERIMENT; HYPERTENSION; IN VIVO STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; PLASMA CONCENTRATION-TIME CURVE; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADENOSINE; ADMINISTRATION, ORAL; ADULT; AREA UNDER CURVE; ARYL HYDROCARBON HYDROXYLASES; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; DRUG INTERACTIONS; FEMALE; HALF-LIFE; HUMANS; MALE; PURINERGIC P2Y RECEPTOR ANTAGONISTS; TOLBUTAMIDE; YOUNG ADULT;

EID: 84876260597     PISSN: 09461965     EISSN: None     Source Type: Journal    
DOI: 10.5414/CP201749     Document Type: Article

References (30)

1. Brilinta™, US full prescribing information, July 2011. Available from URL: http://www.accessdata.fda.gov/drugsatfda-docs/label/2011/ 022433s000lbl.pdf; accessed February 20; 2012.
2. Brilique, summary of product characteristics, 2010. Available from URL: http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Product-Information/ human/001241/WC500100494.pdf; accessed February 20; 2012.
3. Husted S, van Giezen JJ. Ticagrelor: the first reversibly binding oral P2Y12 receptor antagonist. Cardiovasc Ther. 2009; 27: 259-274. doi:10.1111/j.1755-5922.2009.00096.x
4. Wallentin L, Becker RC, Budaj A, Cannon C P, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey K W, Scirica BM, Skene A, Steg PG, Storey R F, 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. doi:10.1056/NEJMoa0904327
5. Taneva E, Bogdanova V, Shtereva N. Acute coronary syndrome, comorbidity, and mortality in geriatric patients. Ann N Y Acad Sci. 2004; 1019: 106-110. doi:10.1196/annals.1297.019
6. Ament P W, Bertolino JG, Liszewski JL. Clinically significant drug interactions. Am Fam Physician. 2000; 61: 1745-1754.
7. Food and Drug Administration. Drug interaction studies - study design, data analysis, and implications for dosing and labelling. September 2006. Available from URL: http://www.fda.gov/downloads/Drugs/.../Guidances/ucm072101. pdf.%20%20Accessed%2030%20August%202011; accessed February 20; 2012.
8. Zhou S F, Zhou Z W, Yang L P, Cai JP. Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009; 16: 3480-3675. doi:10.2174/092986709789057635
9. 12) independently from ADP but antagonizes ADP-induced receptor signaling and platelet aggregation. J Thromb Haemost. 2009; 7: 1556-1565. doi:10.1111/j.1538- 7836.2009.03527.x
10. 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. doi:10.1124/dmd.110.032250
11. 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. doi:10.1124/dmd.110.037143
12. Tattersall R. Traditional pharmacological management of non-insulin-dependent diabetes. Clin Invest Med. 1995; 18: 288-295.
13. Peart G F, Boutagy J, Shenfeld GM. Lack of relationship between tolbutamide metabolism and debrisoquine oxidation phenotype. Eur J Clin Pharmacol. 1987; 33: 397-402. doi:10.1007/BF00637637
14. Miners JO, Birkett DJ. Use of tolbutamide as a substrate probe for human hepatic cytochrome P450 2C9. Methods Enzymol. 1996; 272: 139-145. doi:10.1016/S0076-6879(96)72017-7
15. Jorga KM, Fotteler B, Gasser R, Banken L, Birnboeck H. Lack of interaction between tolcapone and tolbutamide in healthy volunteers. J Clin Pharmacol. 2000; 40: 544-551. doi:10.1177/00912700022009161
16. Tolbutamide, summary of product characteristics, 2011. Available from URL: http://www.medicines.org.uk/emc/medicine/24284/SPC/ tolbutamide%20tablets%20bp%20500mg/; accessed February 20; 2012.
17. 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. doi:10.1016/j. jchromb.2010.06.018
18. Goldberg RJ, Currie K, White K, Brieger D, Steg PG, Goodman SG, Dabbous O, Fox KA, Gore JM. Six-month outcomes in a multinational registry of patients hospitalized with an acute coronary syndrome (the Global Registry of Acute Coronary Events [GRACE]). Am J Cardiol. 2004; 93: 288-293. doi:10.1016/j. amjcard.2003.10.006
19. Andersson TB, Bredberg E, Ericsson H, Sjöberg H. An evaluation of the in vitro metabolism data for predicting the clearance and drug-drug interaction potential of CYP2C9 substrates. Drug Metab Dispos. 2004; 32: 715-721. doi:10.1124/dmd.32.7.715
20. Ito K, Brown HS, Houston JB. Database analyses for the prediction of in vivo drug-drug interactions from in vitro data. Br J Clin Pharmacol. 2004; 57: 473-486. doi:10.1111/j.1365-2125.2003.02041.x
21. Glaeser H. Importance of P-glycoprotein for drug-drug interactions. Handbook Exp Pharmacol. 2011; 201: 285-297. doi:10.1007/978-3-642-14541-4-7
22. Butler K, Teng R. Pharmacokinetics, pharmacody-namics, safety and tolerability of multiple ascending doses of ticagrelor in healthy volunteers. Br J Clin Pharmacol. 2010; 70: 65-77. doi:10.1111/j.1365-2125.2010.03669.x
23. Storey R F, Husted S, Harrington RA, Heptinstall S, Wilcox RG, Peters G, Wickens M, Emanuelsson H, Gurbel P, Grande P, Cannon CP. 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. doi:10.1016/j.jacc.2007.07.058
24. Butler K, Teng R. Effect of ticagrelor on the pharmacokinetics of ethinyl oestradiol and levonorgestrel in healthy volunteers. Curr Med Res Opin. 2011; 27: 1585-1593. doi:10.1185/03007995.201 1.595780
25. Teng R, Mitchell P, Butler K. Pharmacokinetic interaction studies of co-administration of ticagrelor and atorvastatin or simvastatin in healthy volunteers. Eur J Clin Phamacol. 2012; [epub ahead of print on August 25, 2012].
26. He SM, Zhou Z W, Li X T, Zhou SF. Clinical drugs undergoing polymorphic metabolism by human cytochrome P450 2C9 and the implication in drug development. Curr Med Chem. 2011; 18: 667-713. doi:10.2174/092986711794480131
27. Joy MS, Dornbrook-Lavender K, Blaisdell J, Hilliard T, Boyette T, Hu Y, Hogan SL, Candiani C, Falk RJ, Goldstein JA. CYP2C9 genotype and pharmacodynamic responses to losartan in patients with primary and secondary kidney diseases. Eur J Clin Pharmacol. 2009; 65: 947-953. doi:10.1007/s00228-009-0707-7
28. Neuvonen PJ. Drug interactions with HMG-CoA reductase inhibitors (statins): the importance of CYP enzymes, transporters and pharmacogenetics. Curr Opin Investig Drugs. 2010; 11: 323-332.
29. Werner D, Werner U, Meybaum A, Schmidt B, Umbreen S, Grosch A, Lestin HG, Graf B, Zolk O, Fromm MF. Determinants of steady-state torasemide pharmacokinetics: impact of pharmacogenetic factors, gender and angiotensin II receptor blockers. Clin Pharmacokinet. 2008; 47: 323-332. doi:10.2165/00003088- 200847050-00003
30. Palikhe NS, Kim S-H, Nam YH, Ye Y-M, Park H-S. Polymorphisms of aspirin-metabolizing enzymes CYP2C9, NAT2, and UGT1A6 in aspirin-intolerant urticaria. Allergy Asthma Immunol Res. 2011; [epub ahead of print on July 2011].