Airway selectivity: An update of pharmacokinetic factors affecting local and systemic disposition of inhaled steroids

Basic and Clinical Pharmacology and Toxicology

Volumn 98, Issue 6, 2006, Pages 523-536

  Edsbäcker, Staffan ^a   Johansson, Carl Johan ^a  

^a ASTRAZENECA R AND D   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

BECLOMETASONE DIPROPIONATE; BUDESONIDE; BUDESONIDE OLEATE; BUDESONIDE PALMITATE; BUTIXOCORT PROPIONATE; CHLOROFLUOROCARBON; CICLESONIDE; CORTICOSTEROID; DEXAMETHASONE; DRUG METABOLITE; FLUNISOLIDE; FLUOCORTIN BUTYL; FLUORINATED HYDROCARBON; FLUTICASONE PROPIONATE; GAMMA BUTYROLACTONE; HYDROCORTISONE; ITROCINONIDE; LOTEPREDNOL ETABONATE; MOMETASONE FUROATE; PRODRUG; PROPELLANT; ROFLEPONIDE PALMITATE; SOFTDRUG; STEROID; TRIAMCINOLONE ACETONIDE; UNCLASSIFIED DRUG;

ADRENAL DISEASE; AIRWAY; ANTIINFLAMMATORY ACTIVITY; ASTHMA; CLINICAL TRIAL; DRUG DELIVERY SYSTEM; DRUG DISPOSITION; DRUG EFFICACY; DRUG FORMULATION; DRUG RECEPTOR BINDING; DRUG RETENTION; DRUG SAFETY; DRUG SELECTIVITY; ESTERIFICATION; GROWTH RETARDATION; HUMAN; MOUTH DISEASE; NONHUMAN; PHARYNX DISEASE; PLASMA PROTEIN BINDING; PRIORITY JOURNAL; RHINITIS; SHORT SURVEY; TARGET ORGAN;

ADMINISTRATION, INHALATION; ADRENAL CORTEX HORMONES; HUMANS; KINETICS; RESPIRATORY SYSTEM; STEROIDS;

EID: 33646740631     PISSN: 17427835     EISSN: 17427843     Source Type: Journal    
DOI: 10.1111/j.1742-7843.2006.pto_355.x     Document Type: Short Survey

References (89)

1. Agertoft L. S. Pedersen : Lower-leg growth rate and HPA-axis function in children with asthma during treatment with inhaled ciclesonide. J. Allergy Clin. Immunol. 2005, 115, 940 945.
2. Agertoft L. S. Pedersen : Lung deposition and systemic availability of fluticasone Diskus and budesonide Turbuhaler in children. Amer. J. Respir. Crit. Care Med. 2003, 168, 779 782.
3. Agertoft L. S. Pedersen : Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. New Engl. J. Med. 2000, 343, 1064 1069.
4. Andersson P. Å. Ryrfeldt : Biotransformation of the topical glucocorticoids budesonide and beclomethasone 17β,21-dipropionate in human liver and lung homogenate. J. Pharm. Pharmacol. 1984, 36, 763 765.
5. Andersson T. R. Aalbers L. Asking : High nonrespiratory fraction of drug delivered by Diskus compared with Turbuhaler correlates with elevated side-effects levels. Eur. Respir. J. 2004, 24 suppl. 48 584s,.
6. Anttila S. J. Hukkanen J. Hakkola T. Stjernwall P. Beaune R. J. Edwards A. R. Boobis O. Pelkonen H. Raunio : Expression and localization of CYP3A4 and CYP3A5 in human lung. Amer. J. Respir. Cell. Mol. Biol. 1997, 16, 242 249.
7. Axelsson B. P. Bäckman P. Strandberg R. Brattsand : Development of inhaled steroids based upon prodrugs with prolonged intraluminal retention time. In : Inhaled steroids in asthma. Eds.: R. P. Schleimer P. M. O'Byrne S. J. Szefler R. Brattsand. Marcel Dekker, New York, 2002, pp. 565 576.
8. Barnes P. J. I. Adcock : Anti-inflammatory actions of steroids: molecular mechanisms. Trends Pharmacol. Sci. 1993, 14, 436 441.
9. Barnes P. J. S. Pedersen W. Busse : Efficacy and safety of inhaled corticosteroids. Amer. J. Respir. Crit. Care Med. 1998, 157, 1 53.
10. Belvisi M. G. T. J. Brown S. Wicks M. L. Foster : New glucocorticosteroids with an improved therapeutic ratio? Pulm. Pharmacol. Therap. 2001, 14, 221 227.
11. Bend J. R. C. J. Serabijt-Singh R. M. Philpot : The pulmonary uptake, accumulation, and metabolism of xenobiotics. Annu. Rev. Pharmacol. Toxicol. 1985, 25, 97 125.
12. Bethke T. D. R. Nave K. Zech K. A. Gunawardena : Pharmacokinetics of ciclesonide and its active principle in asthma patients and healthy subjects after single-dose inhalation. J. Allergy Clin. Immunol. 2003, 111 suppl. S217 1999, 54 suppl. 40 97 103.
13. Borgström L. T. Bengtsson E. Derom R. Pauwels : Variability in lung deposition of inhaled drug, within and between asthmatic patients, with a pMDI and a dry powder inhaler, Turbuhaler. Int. J. Pharm. 2000, 193, 227 230.
14. Brattsand R. : What factors determine anti-inflammatory activity and selectivity of inhaled steroids? Eur. Respir. Rev. 1997, 7, 356 361.
15. Brutsche M. H. I. C. Brutsche M. Munawar S. J. Langley C. M. Masterson P. T. Daley-Yates R. Brown A. Custovic A. Woodcock : 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.
16. Chapman K. R. P. Patel A. D. D'Urzo M. Alexander S. Mehra C. Oedekoven R. Engelstätter L. P. Boulet : Maintenance of asthma control by once-daily inhaled ciclesonide in adults with persistent asthma. Allergy 2005, 60, 330 337.
17. Chivers J. E. N. H. Holden P. J. Barnes L. E. Donnelly R. Newton : Analysis of dissociated steroid, RU24858, does not exclude a role for inducible genes in the anti-inflammatory actions of glucocorticoids. Amer. J. Respir. Crit. Care Med. 2005, 171 suppl. A223.
18. Dahlström K. P. Larsson : Lung deposition and systemic availability of budesonide inhaled as nebulised suspension from different nebulisers. J. Aerosol Med. 1995, 8, 79.
19. Daley-Yates P. T. A. J. Harker S. Taylor M. J. Daniel : Plasma protein binding (PPB) of corticosteroids (CS): Reappraisal of its significance in systemic pharmacological activity. J. Allergy Clin. Immunol. 2005, 115 suppl. 2 S4 Price J. R. Sisson A. Pereira N. Dallow : Beclomethasone dipropionate: absolute bioavailability, pharmacokinetics and metabolism following intravenous, oral, intranasal and inhaled administration in man. Brit. J. Clin. Pharmacol. 2001, 51, 400 409.
20. Derendorf H. G. Hochhaus S. Krishnaswami H. Möllmann : Systemic disposition and effects of inhaled corticosteroids. In : Inhaled steroids in asthma: optimizing effects in the airways. Eds.: R. P. Schleimer P. M. O'Byrne S. J. Szefler R. Brattsand. Dekker, New York, 2002, pp. 247 272.
21. Derks G. M. G. A. T. Weeks R. S. Mehta M. Beerahee A. Sousa P. T. Daley-Yates : Systemic effects, bioavailability, and pharmacokinetics of fluticasone propionate (FP) diskus and mometasone furoate (MF) twisthaler in healthy and asthmatic subjects. J. Allergy Clin. Immunol. 2005, 115 suppl. 2 S209 Howells J. P. H. Shield A. Prendiville P. S. Ward E. C. Crowne : Symptomatic adrenal insufficiency presenting with hypoglycaemia in children with asthma receiving high dose inhaled fluticasone propionate. Brit. Med. J. 2002, 324, 1081 1083.
22. Edsbäcker S. M. Jendbro : Modes to achieve topical selectivity of inhaled corticosteroid - focus on budesonide. In : Respiratory drug delivery VI. Interpharm Press Inc., Buffalo Grove, Illinois, USA, 1998, pp. 71 82.
23. Edsbäcker S. : Pharmacological factors that influence the choice of inhaled corticosteroids. Drugs 1999, 58 suppl. 4 7 16.
24. Engelstätter R. D. Banerji V. W. Steinijans W. Wurst : Low incidence of oropharyngeal adverse events in asthma patients treated with ciclesonide: results from a pooled analysis. Amer. J. Respir. Crit. Care Med. 2004, 169 suppl. 7 A92.
25. Esmailpour N. P. Högger P. Rohdewald : Binding kinetics of budesonide to the human glucocorticoid receptor. Eur. J. Pharm. Sci. 1998, 6, 219 223.
26. Falk-Nilsson H. H. Gullstrand P. Sjölin S. H. Korn H. Jagfeldt A. Miller-Larsson : Greater esterification and retention of budesonide in the airways and lung as compared to ciclesonide after repeated intratracheal administration in vivo. Amer. J. Respir. Crit. Care Med. 2004, 169 suppl. 7 A92.
27. Fardon T. C. D. K. C. Lee K. Haggart L. C. McFarlane B. J. Lipworth : Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate. Amer. J. Respir. Crit. Care Med. 2004, 170, 960 966.
28. Foe K. K. Brown J. P. Seale : Metabolism kinetics of beclomethasone propionate esters in the homogenates of human lung and liver, whole blood and plasma in vitro. Annual Scientific Meeting of the Thoracic Society of Australia and New Zealand. Canberra, ACT, 1999.
29. Grahnén A. B. Jansson R. M. Brundin A. Ling-Andersson A. Lönnebo M. Johansson S. Å. Eckernäs : A dose-response study comparing suppression of plasma cortisol induced by fluticasone propionate from Diskhaler and budesonide from Turbuhaler. Eur. J. Clin. Pharmacol. 1997, 52, 261 267.
30. Gullstrand H. H. Falk Nilsson A. Smailagic P. Sjölin D. Silberstein A. Miller-Larsson : Esterification and the ratio between airway and peripheral tissue concentrations are greater for budesonide than ciclesonide after intratracheal instillation into rats. Unknown metabolite of ciclesonide in lung. Amer. J. Respir. Crit. Care Med. 2005, 171 suppl. A354.
31. Harrison T. W. A. E. Tattersfield : Plasma concentrations of fluticasone propionate and budesonide following inhalation from dry powder inhalers by healthy and asthmatic subjects. Thorax 2003, 58, 258 260.
32. Harrison T. W. A. Wisniewski J. Honour A. E. Tattersfield : Comparison of the systemic effects of fluticasone propionate and budesonide given by dry powder inhaler in healthy and asthmatic subjects. Thorax 2001, 56, 186 191.
33. Hochberg R. B. S. L. Pahuja J. E. Zielinski J. M. Larner : Steroidal fatty acid esters. J. Steroid Biochem. Mol. Biol. 1991, 40, 577 585.
34. Hochhaus G. H. Möllmann H. Derendorf R. J. Gonzalez-Rothi : Pharmacokinetic/pharmacodynamic aspects of aerosol therapy using glucocorticoids as a model. J. Clin. Pharmacol. 1997, 37, 881 892.
35. Högger P. I. Rawert P. Rohdewald : Dissolution, tissue binding and kinetics of receptor binding of inhaled glucocorticoids. Eur. Respir. J. 1993, 6 suppl. 17 584.
36. Högger P. P. Rohdewald : Glucocorticoid receptors and fluticasone propionate. Rev. Contemporary Pharmacotherapy 1998, 9, 501 522.
37. Högger P. : Dose response and therapeutic index of inhaled corticosteroids in asthma. Curr. Opin. Pulm. Med. 2003, 9, 1 8.
38. Hyland M. E. : Rationale for once-daily therapy in asthma. Compliance issues. Drugs 1999, 58 suppl. 4 1 6.
39. Jendbro M. C.-J. Johansson P. Strandberg H. Falk-Nilsson S. Edsbäcker : Pharmacokinetics of budesonide and its major ester metabolite after inhalation and intravenous administration of budesonide in the rat. Drug Metab. Disp. 2001, 29, 769 776.
40. Johansson C. J. O. Sternebring S. Edsbäcker : Pharmacokinetic Factors Affecting Airway Selectivity of Inhaled Steroids - Role of Prodrug Conversion and Absorption. Amer. J. Respir. Crit. Care Med. 2004, 169, A37.
41. Johnsson M. : Fluticasone propionate: pharmacokinetic and pharmacodynamic implications of different aerosol delivery systems. In : Respiratory drug delivery VI. Interpharm Press Inc., Buffalo Grove, Illinois, USA, 1998, pp. 61 70.
42. Jonasson G. K.-H. Carlsen C. Hultquist : Low-dose budesonide improves exercise-induced bronchospasm in school children. Pediatr. Allergy Immunol. 2000, 11, 120 125.
43. Kaiser H. D. Aaronson R. Dockhorn S. Edsbäcker P. Korenblat A. Källen : Dose-proportional pharmacokinetics of budesonide inhaled via Turbuhaler. Brit. J. Clin. Pharmacol. 1999, 48, 309 316.
44. Källén A. L. Thorsson : The elimination rate of fluticasone is not affected by route of administration. Amer. J. Respir. Crit. Care Med. 1999, 159, A118.
45. Kelly H. W. : Pharmaceutical characteristics that influence the clinical efficacy of inhaled corticosteroids. Ann. Allergy, Asthma Immunol. 2003, 91, 326 334.
46. Kraft M. R. J. Martin S. Wilson R. Djukanovic S. T. Holgate : Lymphocyte and eosinophil influx into alveolar tissue in nocturnal asthma. Amer. J. Respir. Crit. Care Med. 1999, 159, 228 234.
47. Leach C. L. P. Davidson J. Vanden Burgt : Breath-actuated MDI delivers 60% airway deposition with a new CFC-free beclomethasone formulation. Eur. Respir. J. 1996, 9 suppl. 23 255.
48. Lee D. K. K. Haggart G. P. Currie C. E. Bates B. J. Lipworth : Effects of hydrofluoroalkane formulations of ciclesonide 400 microg once daily vs fluticasone 250 microg twice daily on methacholine hyper-responsiveness in mild-to-moderate persistent asthma. Brit. J. Clin. Pharmacol. 2004, 58, 26 33.
49. Lipworth B. J. C. M. Jackson : Safety of inhaled and intranasal corticosteroids: lessons for the new millennium. Drug Safety 2000, 23, 11 33.
50. Lipworth B. J. : Systemic adverse effects of inhaled corticosteroid therapy: a systematic review and meta-analysis. Arch. Internal Med. 1999, 159, 941 955.
51. Maassen van den Brink K. I. I. J. Staal-van den Brekel M. Boorsma S. Edsbäcker E. F. M. Wouters L. Thorsson : In vivo esterification of budesonide in humans. Amer. J. Respir. Crit. Care Med. 2005, 171 suppl. A352.
52. Mendes E. S. A. Pereira I. Danta R. C. Duncan A. Wanner : Comparative bronchial vasoconstrictive efficacy of inhaled glucocorticoids. Eur. Respir. J. 2003, 21, 989 993.
53. Miller-Larsson A. R. Ivarsson H. Mattsson A. Tunek R. Brattsand : High capacity of airway/lung tissue for budesonide esterification as compared to peripheral striated muscles. Eur. Respir. J. 1999, 14 suppl. 30 195s.
54. Miller-Larsson A. H. Mattsson E. Hjertberg M. Dahlbäck A. Tunek R. Brattsand : Reversible fatty acid conjugation of budesonide: novel mechanism for prolonged retention of topically applied steroid in airway tissue. Drug Metab. Disp. 1998, 26, 623 630.
55. Miller-Larsson A. H. Mattsson S. Ohlsson E. Hjertberg M. Dahlbäck A. Tunek R. Brattsand : Prolonged release from the airway tissue of glucocorticoids budesonide and fluticasone propionate as compared to beclomethasone dipropionate and hydrocortisone. Amer. J. Respir. Crit. Care Med. 1994, 149, A466.
56. Minto C. B. Li B. Tattam K. Brown J. P. Seale R. Donnelly : Pharmacokinetics of epimeric budesonide and fluticasone propionate after repeat dose inhalation - intersubject variability in systemic absorption from the lung. Brit. J. Clin. Pharmacol. 2000, 50, 116 124.
57. Mortimer K. T. W. Harrison Y. Tang K. Wu G. Hochhaus A. E. Tattersfield : Plasma concentrations of fluticasone and budesonide following inhalation: the effect of methacholine induced airflow obstruction. Thorax 2004, 59 suppl. 2 10 1 2002, 110, S141 219.
58. Nave R. R.-P. Hummel A. Wohlsen R. Herzog K. Zech : The active metabolite of ciclesonide, des-isobutyryl ciclesonide, forms highly lipophilic fatty acid conjugates in precision-cut rat lung slices. Amer. J. Respir. Crit. Care Med. 2004, 169, A37.
59. Pacifici G. M. M. A. Ferroni A. Temellini A. Gucci M. C. Morelli L. Giuliani : Human liver budesonide sulphotransferase is inhibited by testosterone and correlates with testosterone sulphotransferase. Eur. J. Clin. Pharmacol. 1994, 46, 49 54.
60. Pardridge W. M. : Transport of protein-bound hormones into tissues in vivo. Endocrine Rev. 1981, 2, 103 123.
61. Pardridge W. M. : Plasma protein-mediated transport of steroid and thyroid hormones. Amer. J. Physiol. 1987, 252, E157 E164.
62. Pedersen S. P. M. O'Byrne : A comparison of the efficacy and safety of inhaled steroids in asthma. Allergy 1997, 39 suppl. 52 1 34.
63. Petersen H. A. Kullberg S. Edsbäcker L. Greiff : Nasal retention of budesonide and fluticasone in man: formation of airway mucosal budesonide-esters in vivo. Brit. J. Clin. Pharmacol. 2001, 51, 159 163.
64. Petersen R. L. Agertoft S. Pedersen : Treatment of exercise-induced asthma with beclomethasone dipropionate in children with asthma. Eur. Respir. J. 2004, 24, 932 937.
65. Purucker M.E. C. J. Rosebraugh F. Zhou R. J. Meyer : Inhaled fluticasone propionate by Diskus in the treatment of asthma: a comparison of the efficacy and safety of the same nominal dose given either once or twice a day. Chest 2003, 124, 1584 1593.
66. Richards J. C. G. R. Pitcairn S. Sista : A scintigraphic study to assess the deposition of flunisolide delivered by HFA and CFC metered dose inhalers. In : Respiratory drug delivery VI. Interpharm Press Inc., Buffalo Grove, Illinois, USA, 1998, pp. 405 406.
67. Richter K. F. Kanniess C. Biberger R. Nave H. Magnussen : Comparison of the oropharyngeal deposition of inhaled ciclesonide and fluticasone propionate in patients with asthma. J. Clin. Pharmacol. 2005, 45, 146 152.
68. Rohatagi S. S. Appajosyula H. Derendorf S. Szefler R. Nave K. Zech D. Banerji : Risk-benefit value of inhaled glucocorticoids: a pharmacokinetic/ pharmacodynamic perspective. J. Clin. Pharmacol. 2004, 44, 37 47.
69. Rohatagi S. Y. Luo L. Shen Z. Guo C. Schemm Y. Huang K. Chen M. David R. Nave S. P. King : Protein binding and its potential for eliciting minimal systemic effects with a novel inhaled corticosteroid, ciclesonide. Amer. J. Therapeut. 2005, 12, 201 209.
70. Rohdewald P. M. von Eiff G. Würthwein : Activation of beclomethasone dipropionate in bronchial secretion and receptor affinities and solubility of inhalative applied glucocorticoids. Atemwegs und Lungenkrankheiten 1990, 16, 79 84.
71. Sahasranam S. M. Issar G. Toth G. Horvath G. Hochhaus : Characterization of degradation products of mometasone furoate. Pharmazie 2004, 59, 367 373.
72. Schleimer R. P. : Potential regulation of inflammation in the lung by local metabolism of hydrocortisone. Amer. J. Respir. Cell. Mol. Biol. 1991, 4, 166 173.
73. Selroos O. S. Edsbäcker C. Hultquist : Once-daily inhaled budesonide for the treatment of asthma: Clinical evidence and pharmacokinetic explanation. J. Asthma 2004, 41, 771 790.
74. Sheffer A. L. M. Silverman A. J. Woolcock P. V. Díaz B. Lindberg B. Lindmark : Long-term safety of once-daily budesonide in patients with early-onset mild persistent asthma: results of the Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study. Ann. Allergy, Asthma Immunol. 2005, 94, 48 54.
75. Simkin P. A. M. P. Wu D. M. Foster : Articular pharmacokinetics of protein-bound antirheumatic agents. Clin. Pharmacokin. 1993, 25, 342 350.
76. Subbarao P. J. M. Duong J. Otis G. Obminski E. Ädelroth S. Pedersen M. Inman P. M. O'Byrne : Ciclesonide is effective in protecting against exercise-induced bronchoconstriction. J. Allergy Clin. Immunol. 2005, 115 suppl. 2 S1 R. J. Martin : Distal lung inflammation in asthma. Ann. Allergy, Asthma Immunol. 2002, 89, 119 124.
77. Thalén A. P. H. Andersson P. T. Andersson B. Axelsson S. Edsbäcker R. Brattsand : Prospects for developing inhaled steroids with extrahepatic metabolism "soft steroids". In : Inhaled steroids in asthma: optimizing effects in the airways. Eds.: R. P. Schleimer P. M. O'Byrne S. J. Szefler R. Brattsand. Dekker, New York, 2002, pp. 521 540.
78. Thorsson L. S. Edsbäcker T.-B. Conradsson : Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered-dose inhaler (pMDI). Eur. Respir. J. 1994, 7, 1839 1844.
79. Thorsson L. S. Edsbäcker A. Källén C. G. Löfdahl : Pharmacokinetics and systemic activity of fluticasone via Diskus and pMDI, and of budesonide via Turbuhaler. Brit. J. Clin. Pharmacol. 2001, 52, 529 538.
80. Thorsson L. S. Edsbäcker : Lung deposition of budesonide from a pressurized metered dose inhaler attached to a spacer. Eur. Respir. J. 1998, 12, 1340 1345.
81. Thorsson L. S. Edsbäcker : Lung uptake of budesonide via Turbuhaler is greater than that of fluticasone propionate via Diskus or pMDI. Amer. J. Respir. Crit. Care Med. 1999, 59 suppl. 3 A118.
82. Todd G. K. Dunlop J. McNaboe M. F. Ryan D. Carson M. D. Shields : Growth and adrenal suppression in asthmatic children treated with high-dose fluticasone propionate. Lancet 1996, 348, 27 29.
83. Tunek A. K. Sjödin G. Hallström : Reversible formation of fatty acid esters of budesonide, an antiasthma glucocorticoid, in human lung and liver microsomes. Drug Metab. Disp. 1997, 11, 1311 1317.
84. Valotis A. K. Neukam O. Elert P. Högger : Human receptor kinetics, tissue binding affinity, and stability of mometasone furoate. J. Pharmaceut. Sci. 2004, 93, 1337 1350.
85. Wardlaw A. J. S. Dunnette G. J. Gleich J. V. Collins A. B. Kay : Eosinophils and mast cells in bronchoalveolar lavage in subjects with mild asthma: relationship to bronchial hyperreactivity. J. Allergy Clin. Immunol. 1988, 88, 935 942.
86. Weiner P. N. Berar-Yanay A. Davidovich R. Magadle : Nocturnal cortisol secretion in asthmatic patients after inhalation of fluticasone propionate. Chest 1999, 116, 931 934.
87. Wieslander E. E.-L. Delander L. Järkelid E. Hjertberg A. Tunek R. Brattsand : Pharmacologic importance of the reversible fatty acid conjugation of budesonide studied in a rat cell line in vitro. Amer. J. Respir. Cell. Mol. Biol. 1998, 19, 477 484.
88. Wieslander E. E.-L. Delander H. Mattsson A. Tunek R. Brattsand : Modulation of fatty acid esterification of budesonide by the GR antagonist RU486 and the ACAT-inhibitor cyclandelate in vitro. Amer. J. Respir. Crit. Care Med. 1999, 159 suppl. 3 A114.
89. Willey J. C. E. Coy C. Brolly M. J. Utell M. W. Frampton J. Hammersley W. G. Thilly D. Olson K. Cairns : Xenobiotic metabolism enzyme gene expression in human bronchial epithelial and alveolar macrophage cells. Amer. J. Respir. Cell. Mol. Biol. 1996, 14, 262 271.