Risk-Benefit Value of Inhaled Glucocorticoids: A Pharmacokinetic/Pharmacodynamic Perspective

Journal of Clinical Pharmacology

Volumn 44, Issue 1, 2004, Pages 37-47

  Rohatagi, Shashank ^a   Appajosyula, Sireesh ^a   Derendorf, Hartmut ^b   Szefler, Stanley ^c   Nave, Buediger ^d   Zech, Karl ^d   Banerji, Donald ^a  

^a SANOFI   (France)

^b UNIVERSITY OF FLORIDA   (United States)

^c NATIONAL JEWISH MEDICAL AND RESEARCH CENTER   (United States)

^d ALTANA Pharma   (Germany)

Author keywords

Asthma; Inhaled glucocorticoids; Pharmacodynamics; Pharmacokinetics; Risk benefit value

Indexed keywords

BECLOMETASONE; BECLOMETASONE DIPROPIONATE; BUDESONIDE; CHLOROFLUOROCARBON; CICLESONIDE; FLUNISOLIDE; FLUORINATED HYDROCARBON; FLUTICASONE PROPIONATE; GLUCOCORTICOID; MOMETASONE FUROATE;

ADRENAL SUPPRESSION; ASTHMA; CLINICAL TRIAL; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG CONJUGATION; DRUG EFFICACY; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG RECEPTOR BINDING; DRUG RETENTION; DRUG SAFETY; DRUG TARGETING; HUMAN; LUNG; METERED DOSE INHALER; PARTICLE SIZE; PHARMACODYNAMICS; REVIEW; RISK BENEFIT ANALYSIS; SIDE EFFECT;

ADMINISTRATION, INHALATION; ASTHMA; BIOLOGICAL AVAILABILITY; CHEMISTRY, PHARMACEUTICAL; GLUCOCORTICOIDS; HALF-LIFE; HUMANS; METABOLIC CLEARANCE RATE; PROTEIN BINDING; RECEPTORS, GLUCOCORTICOID; RISK ASSESSMENT;

EID: 0345733708     PISSN: 00912700     EISSN: None     Source Type: Journal    
DOI: 10.1177/0091270003260334     Document Type: Review

References (78)

1. World Health Organization: WHO fact sheet no 206. Last accessed March 1, 2002, from www.who.int/int-fs/en/fact206.html.2000
2. Global initiative for asthma: global strategy for asthma and prevention. Last accessed March 11, 2002, from www.ginaasthma.com/home/index.htm.2002
3. NAEPP expert panel report guidelines for the diagnosis and management of asthma: update on selected topics 2002. Last accessed September 5, 2002, from www.nhlbi.nih.gov/guidelines/asthma/index.htm.2002
4. Donahue JG, Weiss ST, Livingston JM, Goetsch MA, Greineder DK, Platt R: Inhaled steroids and the risk of hospitalization for asthma. JAMA 1997;277(11):887-891.
5. Laitinen LA, Laitinen A, Haahtela T: A comparative study of the effects of an inhaled corticosteroid, budesonide, and a beta 2-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: a randomized, double-blind, parallel-group controlled trial. J Allergy Clin Immunol 1992;90(1):32-42.
6. Mak VH, Melchor R, Spiro SG: Easy bruising as a side-effect of inhaled corticosteroids. Eur Respir J 1992;5(9):1068-1074.
7. Brown PH, Greening AP, Crompton GK: Large volume spacer devices and the influence of high dose beclomethasone dipropionate on hypothalamo-pituitary-adrenal axis function. Thorax 1993;48(3):233-238.
8. Wise R, Connett J, Weinmann G, Scanlon P, Skeans M: Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. N Engl J Med 2000;343(26):1902-1909.
9. Lipworth BJ: Systemic adverse effects of inhaled corticosteroid therapy: a systematic review and meta-analysis. Arch Intern Med 1999;159(9):941-955.
10. Martin RJ, Szefler SJ, Chinchilli VM, Kraft M, Dolovich M, Boushey HA, et al: Systemic effect comparisons of six inhaled corticosteroid preparations. Am J Respir Crit Care Med 2002;165(10):1377-1383.
11. Lipworth BJ, Wilson BJ: Dose response to inhaled corticosteroids. Semin Resp Crit Care 1998;19:625-646.
12. Kelly HW: Establishing a therapeutic index for the inhaled corticosteroids: Part I. Pharmacokinetic/pharmacodynamic comparison of the inhaled corticosteroids. J Allergy Clin Immunol 1998;102(4, Pt. 2):S36-S51.
13. Derendorf H: Pharmacokinetic and pharmacodynamic properties of inhaled corticosteroids in relation to efficacy and safety. Respir Med 1997;91(Suppl. A):22-28.
14. Rohatagi S, Rhodes GR, Chaikin P: Absolute oral versus inhaled bioavailability: significance for inhaled drugs with special reference to inhaled glucocorticoids. J Clin Pharmacol 1999;39(7):661-663.
15. Mackie AE, McDowall JE, Ventresca P, Bye A, Falcoz C, Daley-Yates PT: Systemic exposure to fluticasone propionate administered via metered-dose inhaler containing chlorofluorocarbon or hydrofluoroalkane propellant. Clin Pharmacokinet 2000;39(Suppl. 1):17-22.
16. Kelly HW: Comparative potency and clinical efficacy of inhaled corticosteroids. Respir Care Clin N Am 1999;5(4):537-553.
17. Daley-Yates PT, Price AC, Sisson JR, Pereira A, Dallow N: Beclomethasone dipropionate: absolute bioavailability, pharmacokinetics and metabolism following intravenous, oral, intranasal and inhaled administration in man. Br J Clin Pharmacol 2001;51(5): 400-409.
18. Dickens GR, Wermeling DP, Matheny CJ, John W, Abramowitz W, Sista SM, et al: Pharmacokinetics of flunisolide administered via metered dose inhaler with and without a spacer device and following oral administration. Ann Allergy Asthma Immunol 2000;84(5):528-532.
19. Ryrfeldt A, Andersson P, Edsbacker S, Tonnesson M, Davies D, Pauwels R: Pharmacokinetics and metabolism of budesonide, a selective glucocorticoid. Eur J Respir Dis Suppl 1982;122:86-95.
20. Derendorf H, Hochhaus G, Rohatagi S, Mollmann H, Barth J, Sourgens H, et al: Pharmacokinetics of triamcinolone acetonide after intravenous, oral, and inhaled administration. J Clin Pharmacol 1995;35(3):302-305.
21. Derendorf H, Hochhaus G, Krishnaswami S, Meibohm B, Mollmann H: Optimized therapeutic ratio of inhaled corticosteroids using retrometabolism. Pharmazie 2000;55(3):223-227.
22. Derendorf H, Hochhaus G, Meibohm B, Mollmann H, Barth J: Pharmacokinetics and pharmacodynamics of inhaled corticosteroids. J Allergy Clin Immunol 1998;101(4, Pt. 2):S440-S446.
23. Falcoz C, Horton J, Mackie AE, Harding SM, Daley-Yates PT: Pharmacokinetics of fluticasone propionate inhaled via the Diskhaler and Diskus powder devices in patients with mild-to-moderate asthma. Clin Pharmacokinet 2000;39(Suppl. 1):31-37.
24. Dolovich M, Rhem R, Gerrard L, Coates G: Lung deposition of coarse CFC vs fine HFA pMDI aerosols of beclomethasone dipropionate (BDP) in asthma [abstract A33]. Am J Crit Care Med 2000;A33:161.
25. Vanden Burgt JA, Busse WW, Martin RJ, Szefler SJ, Donnell D: Efficacy and safety overview of a new inhaled corticosteroid, QVAR (hydrofluoroalkane-beclomethasone extrafine inhalation aerosol), in asthma. J Allergy Clin Immunol 2000;106(6):1209-1226.
26. Mitchell JP, Nagel MW, Archer AD: Size analysis of a pressurized metered dose inhaler-delivered suspension formulation by the API Aerosizer time-of-flight aerodynamic particle size analyzer. J Aerosol Med 1999;12(4):255-264.
27. Leach CL, Davidson PJ, Boudreau RJ. Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone. Eur Respir J 1998;12(6):1346-1353.
28. Lipworth BJ, Jackson CM: Safety of inhaled and intranasal corticosteroids: lessons for the new millennium. Drug Saf 2000;23(1):11-33.
29. Barnes PJ, Pedersen S, Busse WW: Efficacy and safety of inhaled corticosteroids: New developments. Am J Respir Crit Care Med 1998;157(3, Pt. 2):S1-S53.
30. Adcock IM, Gilbey T, Gelder CM, Chung KF, Barnes PJ: Glucocorticoid receptor localization in normal and asthmatic lung. Am J Respir Crit Care Med 1996;154(3, Pt. 1):771-782.
31. Boobis AR: Comparative physicochemical and pharmacokinetic profiles of inhaled beclomethasone dipropionate and budesonide. Respir Med 1998;92(Suppl. B):2-6.
32. Wurthwein G, Rehder S, Rohdeswald P: Lipophilicity and receptor affinity of glucocorticoids. Pharm Zeit Wissensch 1992;137:161-167.
33. Leung DY, Szefler SJ: Diagnosis and management of steroid-resistant asthma. Clin Chest Med 1997;18(3):611-625.
34. Leung DY, Spahn JD, Szefler SJ: Immunologic basis and management of steroid-resistant asthma. Allergy Asthma Proc 1999;20(1):9-14.
35. Mollmann H, Derendorf H, Barth J, Meibohm B, Wagner M, Krieg M, et al: Pharmacokinetic/pharmacodynamic evaluation of systemic effects of flunisolide after inhalation. J Clin Pharmacol 1997;37(10):893-903.
36. Rohatagi S, Bye A, Falcoz C, Mackie AE, Meibohm B, Mollmann H, et al: Dynamic modeling of cortisol reduction after inhaled administration of fluticasone propionate. J Pharmacol 1996;36(10): 938-941.
37. Martin LE, Harrison C, Tanner RJN: Metabolism of beclomethasone dipropionate by animals and man. Postgrad Med J 1975;51(Suppl. 4):11-20.
38. Rowland M, Tozer TN: Clinical Pharmacokinetics: Concepts and Applications. 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 1995.
39. QVAR prescribing information, 2001. Available: PDR Online ww.gvar.com
40. Falcoz C, Kirby SM, Smith J, Olsson P, Ventresca GP: Pharmacokinetics and systemic exposure of inhaled beclomethasone dipropionate [abstract]. Eur Respir J 1996;5(9):1062.
41. Lund-Pero M, Jeppson B, Arneklo-Nobin B, Sjogren HO, Holmgren K, Pero RW: Non-specific steroidal esterase activity and distribution in human and other mammalian tissues. Clin Chim Acta 1994;224(1):9-20.
42. Miller-Larsson A, Mattsson H, Hjertberg E, Dahlback M, Tunek A, Brattsand R: Reversible fatty acid conjugation of budesonide: novel mechanism for prolonged retention of topically applied steroid in airway tissue. Drug Metab Dispos 1998;26(7):623-630.
43. Tunek A, Sjodin K, Hallstrom G: Reversible formation of fatty acid esters of budesonide, an antiasthma glucocorticoid, in human lung and liver microsomes. Drug Metab Dispos 1997;25(11):1311-1317.
44. Falk Nillsen HC, Strandberg P, Brattsand R, Miller-Larsson A: High airway selectivity of budesonide due to endogenous reversible esterification [abstract A586]. Paper presented at the American Thoracic Society International conference, San Francisco, May 18, 2001.
45. Donahue JG. Asthma: new approaches to anti-inflammatory therapy. Pulmonary Perspect, 2001. Retrieved October 5, 2001, from www.chestnet.org/publications/pulmonary.Perspectives/vol2116n2002c
46. Campbell LM, Bodalia B, Gogbashian CA, Gunn SD, Humphreys PJ, Powell JP: Once-daily budesonide: 400 micrograms once daily is as effective as 200 micrograms twice daily in controlling childhood asthma. PETITE Research Group. Int J Clin Pract 1998;52(4):213-219.
47. Chisholm SL, Dekker FW, Knuistingh Neven A, Petri H: Once-daily budesonide in mild asthma. Respir Med 1998;92(3):421-425.
48. Venables TL, Addlestone MB, Smithers AJ, et al: A comparison of the efficacy and patient acceptability of once daily budesonide via Turbohaler and twice daily fluticasone propionate via disc-inhaler at an equal daily dose of 400 μg in adult asthmatics. Br J Clin Res 1996;7:15-32.
49. Miller-Larsson A, Jansson P, Runstrom A, Brattsand R: Prolonged airway activity and improved selectivity of budesonide possibly due to esterification. Am J Respir Crit Care Med 2000;162(4, Pt. 1):1455-1461.
50. Busse WW, Brazinsky S, Jacobson K, et al: Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant. J Allergy Clin Immunol 1999;104(6):1215-1222.
51. Fireman P, Prenner BM, Vincken W, Demedts M, Mol SJ, Cohen RM: Long-term safety and efficacy of a chlorofluorocarbon-free beclomethasone dipropionate extrafine aerosol. Ann Allergy Asthma Immunol 2001;86(5):557-565.
52. Richards J, Hirst P, Pitcairn G, Mahashabde S, Abramowitz W, Nolting A, et al: Deposition and pharmacokinetics of flunisolide delivered from pressurized inhalers containing non-CFC and CFC propellants. J Aerosol Med 2001;14(2):197-208.
53. Corren J, Nelson H, Greos LS, Bensch G, Goldstein M, Wu J, et al: Effective control of asthma with hydrofluoroalkane flunisolide delivered as an extrafine aerosol in asthma patients. Ann Allergy Asthma Immunol 2001;87(5):405-411.
54. Pearlman DS, Noonan MJ, Tashkin DP, Goldstein MF, Hamedani AG, Kellerman DJ, et al: Comparative efficacy and safety of twice daily fluticasone propionate powder versus placebo in the treatment of moderate asthma. Ann Allergy Asthma Immunol 1997;78(4):356-362.
55. Wasserman SI, Gross GN, Schoenwetter WF, Munk ZM, Kral KM, Schaberg A, et al: A 12-week dose-ranging study of fluticasone propionate powder in the treatment of asthma. J Asthma 1996;33(4):265-274.
56. Chervinsky P, van As A, Bronsky EA, Dockhorn R, Noonan M, LaForce C, et al: Fluticasone propionate aerosol for the treatment of adults with mild to moderate asthma. The Fluticasone Propionate Asthma Study Group. J Allergy Clin Immunol 1994;94(4):676-683.
57. Li JT, Ford LB, Chervinsky P, Weisberg SC, Kellerman DJ, Faulkner KG, et al: Fluticasone propionate powder and lack of clinically significant effects on hypothalamic-pituitary-adrenal axis and bone mineral density over 2 years in adults with mild asthma. J Allergy Clin Immunol 1999;103(6):1062-1068.
58. Affrime MB, Kosoglou T, Thonoor CM, Flannery BE, Herron JM: Mometasone furoate has minimal effects on the hypothalamic-pituitary-adrenal axis when delivered at high doses. Chest 2000;118(6):1538-1546.
59. Kemp JP, Berkowitz RB, Miller SD, Murray JJ, Nolop K, Harrison JE: Mometasone furoate administered once daily is as effective as twice-daily administration for treatment of mild-to-moderate persistent asthma. J Allergy Clin Immunol 2000;106(3):485-492.
60. Fish JE, Karpel JP, Craig TJ, Bensch GW, Noonan M, Webb DR, et al: Inhaled mometasone furoate reduces oral prednisone requirements while improving respiratory function and health-related quality of life in patients with severe persistent asthma. J Allergy Clin Immunol 2000;106(5):852-860.
61. Stoeck M, Hatzelmann A, Belvisi MG, Foster ML, Bundschuh DS: In vitro anti-inflammatory activity of the new glucocorticoid ciclesonide in human cells. Eur Respir J 2001;18(Suppl. 33):A679.
62. Taylor DA, Jensen MW, Kanabar V, Engelstatter R, Steinijans VW, Barnes PJ, et al: A dose-dependent effect of the novel inhaled corticosteroid ciclesonide on airway responsiveness to adenosine-5′-monophosphate in asthmatic patients. Am J Respir Crit Care Med 1999;160(1):237-243.
63. Postma DS, Sevette C, Martinat Y, Schlosser N, Aumann J, Kafe H: Treatment of asthma by the inhaled corticosteroid ciclesonide given either in the morning or evening. Eur Respir J 2001;17(6):1083-1088.
64. Dietzel K, Engelstatter R, Keller A: Ciclesonide: An on-site-activated steroid. Prog Respir Res 2001;31:91-93.
65. Derom E, Van de Velde V, Marisenns S, Vincken W, Pauwels RA: Efficacy and systemic effects of ciclesonide and fluticasone in asthma patients. Eur Respir J 2001;18(Suppl. 33):A1015.
66. Bethke TD, Boudreau RJ, Hasselquist BE, Davidson P, Leach CL, Drollmann A, et al: High lung deposition of ciclesonide in 2D and 3D imaging [poster P746]. Paper presented at the European Respiratory Society Annual Congress, Stockholm, Sweden, September 14-18, 2002.
67. Argenti D, Shah B, Heald D: A study comparing the clinical pharmacokinetics, pharmacodynamics, and tolerability of triamcinolone acetonide HFA-134a metered-dose inhaler and budesonide dry-powder inhaler following inhalation administration. J Clin Pharmacol May 2000;40(5):516-526.
68. Thorsson L, Edsbacker S, Conradson TB: Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered-dose inhaler P-MDI. Eur Respir J 1994;7(10):1839-1844.
69. Thorsson L, Edsbacker S: Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer. Eur Respir J 1998;12(6):1340-1345.
70. Thorsson L, Edsbacker S, Kallen A, Lofdahl CG: Pharmacokinetics and systemic activity of fluticasone via Diskus and pMDI, and of budesonide via Turbuhaler. Br J Clin Pharmacol 2001;52(5): 529-538.
71. Mollmann H, Wagner M, Krishnaswami S, Dimova H, Tang Y, Falcoz C, et al: Single-dose and steady-state pharmacokinetic and pharmacodynamic evaluation of therapeutically clinically equivalent doses of inhaled fluticasone propionate and budesonide, given as Diskus or Turbohaler dry-powder inhalers to healthy subjects. J Clin Pharmacol 2001;41(12):1329-1338.
72. Pulmicort prescribing information, 2001. Available: www. twistclickinhale.com/2001
73. Bruns R, Rohdewald P: Time dependent effects of glucocorticoids on adrenocorticotropin secretion of rat pituitaries ex-vivo. J Pharm Pharmacol 2000;52(1):93-98.
74. Smith CL, Kreutner W: In vitro glucocorticoid receptor binding and transcriptional activation by topically active glucocorticoids. Arzneimittelforschung 1998;48(9):956-960.
75. Mackie AE, Ventresca GP, Fuller RW, Bye A: Pharmacokinetics of intravenous fluticasone propionate in healthy subjects. Br J Clin Pharmacol 1996;41(6):539-542.
76. Thorsson L, Dahlstrom K, Edsbacker S, Kallen A, Paulson J, Wiren JE: Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects. Br J Clin Pharmacol 1997;43(2):155-161.
77. Advair prescribing information, 2002. Available: http://us.gsk.com/products/assets/us_advair.pdf.2002
78. Esmailpour N, Hogger P, Rohdewald P: Binding kinetics of budesonide to the human glucocorticoid receptor. Eur J Pharm Sci 1998;6(3):219-223.