The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of inhaled fluticasone furoate and vilanterol trifenatate in healthy subjects

British Journal of Clinical Pharmacology

Volumn 75, Issue 6, 2013, Pages 1478-1487

  Kempsford, Rodger ^a   Allen, Ann ^a   Bal, Joanne ^a   Rubin, David ^b   Tombs, Lee ^c  

^a GLAXOSMITHKLINE   (United Kingdom)

^b GLAXOSMITHKLINE   (United States)

^c Synergy Statistics and Programming   (United Kingdom)

Author keywords

Drug interactions; Fluticasone furoate; Ketoconazole; Vilanterol

Indexed keywords

FLUTICASONE FUROATE; HYDROCORTISONE; KETOCONAZOLE; PLACEBO; POTASSIUM; VILANTEROL TRIFENATATE;

ADULT; AREA UNDER THE CURVE; ARTICLE; CLINICAL LABORATORY; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG INDUCED HEADACHE; ELECTROCARDIOGRAM; FEMALE; HEART RATE; HUMAN; HYDROCORTISONE BLOOD LEVEL; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; PHARMACODYNAMICS; POTASSIUM BLOOD LEVEL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SINGLE DRUG DOSE; VITAL SIGN;

14-ALPHA DEMETHYLASE INHIBITORS; ADMINISTRATION, INHALATION; ADOLESCENT; ADULT; ANDROSTADIENES; BENZYL ALCOHOLS; BRONCHODILATOR AGENTS; CHLOROBENZENES; CROSS-OVER STUDIES; CYTOCHROME P-450 CYP3A; DOUBLE-BLIND METHOD; DRUG INTERACTIONS; FEMALE; HUMANS; KETOCONAZOLE; MALE; MIDDLE AGED; YOUNG ADULT;

EID: 84878135015     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/bcp.12019     Document Type: Article

References (22)

1. Clarke SE, Jones BC. Human cytochromes P450 and their role in metabolism-based drug-drug interactions. In: Drug-Drug Interactions, ed. Rodrigues AD New York: Marcel Dekker, 2002; 55-88.
2. Lötvall J, Bateman ED, Bleecker ER, Busse W, Woodcock A, Follows R, Lim J, Stone S, Jacques L, Haumann B. Dose-related efficacy of vilanterol trifenatate (VI), a long-acting beta2 agonist (LABA) with inherent 24-hour activity, in patients with persistent asthma. Eur Respir J 2010; 36: (Suppl. 54): 1013s.
3. Hanania NA, Feldman G, Zachgo W, Shim JJ, Crim C, Sanford L, Lettis S, Barnhart F, Haumann B. Safety of vilanterol trifenatate (VI) in a COPD dose-ranging study. Chest 2012; 142: 119-127.
4. Kempsford RD, Norris V, Siederer SK. The pharmacodynamics, pharmacokinetics and tolerability of repeat doses of the novel inhaled long-acting beta2 adrenoceptor agonist (LABA) GW642444 (25, 50 and 100mcg) in healthy subjects. Am J Respir Crit Care Med 2010; 181: A4461.
5. van den Berge M, Luijk B, Bareille P, Dallow N, Postma DS, Lammers J-WJ. Prolonged protection of the new inhaled corticosteroid fluticasone furoate against AMP hyperresponsiveness in patients with asthma. Allergy 2010; 65: 1531-1535.
6. Dollery C ed. Ketoconazole. In: Therapeutic Drugs, 2, Edinburgh: Churchill Livingstone, 1991; 21-24.
7. Brindley C, Falcoz C, Makie AE, Bye A. Absorption kinetics after inhalation of fluticasone propionate via the Diskhaler, Diskus and metered-dose inhaler in healthy volunteers. Clin Pharmacokinet 2000; 39: 1-8.
8. Tsunoda SM, Velez RL, von Moltke LL, Greenblatt DJ. Differentiation of intestinal and hepatic cytochrome P450 3A activity with use of midazolam as an in vivo probe: effect of ketoconazole. Clin Pharmacol Ther 1999; 66: 461-471.
9. Gomez DY, Wacher VJ, Tomlanovich SJ, Herbert MF, Benet LZ. The effects of ketoconazole on the intestinal metabolism and bioavailability of cyclosporine. Int J Clin Pharmacol Ther. 1995; 58: 15-19.
10. Zhang L, Zhang Y, Huang SM. Scientific and regulatory perspectives on metabolizing enzyme-transporter interplay and its role in drug interactions: challenges in predicting drug interactions. Mol Pharm 2009; 6: 1766-1774.
11. FDA. 1996 FDA. Guidance for Industry: Drug interaction studies - study design, data analysis and implications for dosing and labelling. Available at http://www.fda.gov/cder/guidance/index.htm (last accessed 14 November 2011).
12. Ward KW, Stelman GJ, Morgan JA, Zeigler KS, Azzarano LM, Kehler JR, McSurdy-Freed JE, Proksch JW, Smith BR. Development of an in vivo preclinical screen model to estimate absorption and first-pass hepatic extraction of xenobiotics. II. Use of ketoconazole to identify P-glycoprotein/CYP3A-limited bioavailability in the monkey. Drug Metab Dispos 2004; 32: 172-177.
13. Kim RB, Wandel C, Leake B, Cvetkovic M, Fromm MF, Dempsey PJ, Roden MM, Belas F, Chaudhary AK, Roden DM, Wood AJ, Wilkinson GR. Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res 1999; 16: 408-414.
14. Prime D, De Backer W, Hamilton M, Cahn A, Preece A, Kelleher D, Lindo E. Comparison of inhalation profiles through a novel dry powder inhaler (nDPI) and lung function measurements for healthy subjects, asthma and chronic obstructive pulmonary disease (COPD) patients. Am J Respir Crit Care Med 2012; 185: A2940.
15. Cekici L, Arschang V, Kohansal R, Burghuber OC. Short-term effects of 2009 Short-term effects of inhaled salbutamol on autonomic cardiovascular control in healthy subjects: a placebo-controlled study. Br J Clin Pharmacol 2009; 67: 394-402.
16. Allen A, Bianco J, Bal J, Tombs L, Kempsford R. The absolute bioavailability of fluticasone furoate (FF) and vilanterol (VI) following inhaled administration in combination in healthy subjects. Eur Respir J 2011; 38: (Suppl. 55): 724s.
17. Robert M, Salvà M, Segarra R, Pavesi M, Esbri R, Roberts D, Golor G. The prokinetic cinitapride has no clinically relevant pharmacokinetic interaction and effect on QT during coadministration with ketoconazole. Drug Metab Dispos 2007; 35: 1149-1156.
18. Nizoral (ketoconazole) Product Information. 2010. Available at http://www.medicines.org.uk/EMC/medicine/912/SPC/Nizoral%20Tablets (last accessed 7 December 2010).
19. Brutsche MH, Brutsche IC, Munavvar M, Langley SJ, Masterson CM, Daley-Yates PT, Brown R, Custovic A, Woodcock A. Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: a randomised crossover study. Lancet 2000; 356: 556-561.
20. Singh DS, Whale C, Houghton N, Daley-Yates P, Kirby SM, Woodcock AA. Pharmacokinetics and systemic effects of inhaled fluticasone propionate in chronic obstructive pulmonary disease. Br J Clin Pharmacol 2003; 55: 375-381.
21. Seretide Product Information. 2011. Available at http://hcp.gsk.com/therapy_areas/respiratory-and-allergy/seretide/542852/ (last accessed 20 September 2012).
22. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/020121s028lbl.pdf (last accessed 19 August 2012).