![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 26, Issue 7, 623-630, July 1998
Departments of
Pharmacology (A.M.-L., M.D., R.B.) and
Kinetics and
Metabolism (H.M., E.H., A.T.), Astra Draco AB
A high airway concentration might be required for the antiasthmatic
efficacy of inhaled glucocorticosteroids (GCS). The topical uptake and
retention of GCS in airway tissue were compared for GCS of the inhaled
type [budesonide (BUD), fluticasone propionate (FP), and
beclomethasone dipropionate (BDP)] and of the noninhaled type
(dexamethasone and hydrocortisone). 3H-labeled
GCS solutions were administered into rat airways by either perfusion of
trachea in vivo, intratracheal instillation, or inhalation.
Radioactivity was determined in the airway tissue, lung parenchyma, and
plasma 20 min to 24 hr after exposure. Ethanol extracts of exposed
tracheas were analyzed by HPLC. Exposed tracheas were also incubated
in vitro in buffer, and the released radioactivity was
analyzed by HPLC. BUD, FP, and BDP were equally well taken up into the
airway tissue; their uptake was 25-130 times greater than that of
dexamethasone and hydrocortisone. BUD was shown to form very lipophilic
intracellular fatty acid esters (at carbon 21) in the airway and lung
tissue after topical application. In large airways 20 min after
administration, approximately 70-80% of retained BUD was conjugated.
BUD stored in esterified form in the tissue was retained in large
airways for a prolonged time, compared with FP and BDP, which do not
form such conjugates. The fatty acid conjugation of BUD is reversible
in vivo; BUD conjugates are gradually hydrolyzed and free
BUD is regenerated. This reversible conjugation may improve airway
selectivity, as well as prolong the local anti-inflammatory action of
BUD in the airways and might be one explanation for why BUD is
efficacious in the treatment of mild asthma when inhaled once daily.
This article has been cited by other articles:
|
|
 |
|
  B. Lindmark Review: Differences in the pharmacodynamics of budesonide/formoterol and salmeterol/fluticasone reflect differences in their therapeutic usefulness in asthma Therapeutic Advances in Respiratory Disease, October 1, 2008; 2(5): 279 - 299. [Abstract] [PDF]
|
|
|
|
 |
|
 T. F. Yeh, H. C. Lin, C. H. Chang, T. S. Wu, B. H. Su, T. C. Li, S. Pyati, and C. H. Tsai Early Intratracheal Instillation of Budesonide Using Surfactant as a Vehicle to Prevent Chronic Lung Disease in Preterm Infants: A Pilot Study Pediatrics, May 1, 2008; 121(5): e1310 - e1318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Lexmuller, H. Gullstrand, B.-O. Axelsson, P. Sjolin, S. H. Korn, D. S. Silberstein, and A. Miller-Larsson Differences in Endogenous Esterification and Retention in the Rat Trachea between Budesonide and Ciclesonide Active Metabolite Drug Metab. Dispos., October 1, 2007; 35(10): 1788 - 1796. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Derendorf Pharmacokinetic and Pharmacodynamic Properties of Inhaled Ciclesonide J. Clin. Pharmacol., June 1, 2007; 47(6): 782 - 789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Derendorf, R. Nave, A. Drollmann, F. Cerasoli, and W. Wurst Relevance of pharmacokinetics and pharmacodynamics of inhaled corticosteroids to asthma. Eur. Respir. J., November 1, 2006; 28(5): 1042 - 1050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Cerasoli Jr Developing the Ideal Inhaled Corticosteroid Chest, July 1, 2006; 130(1_suppl): 54S - 64S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Winkler, G. Hochhaus, and H. Derendorf How the Lung Handles Drugs: Pharmacokinetics and Pharmacodynamics of Inhaled Corticosteroids Proceedings of the ATS, December 1, 2004; 1(4): 356 - 363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rohatagi, S. Appajosyula, H. Derendorf, S. Szefler, R. Nave, K. Zech, and D. Banerji Risk-Benefit Value of Inhaled Glucocorticoids: A Pharmacokinetic/Pharmacodynamic Perspective J. Clin. Pharmacol., January 1, 2004; 44(1): 37 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. K. Kraft, B. Steiger, D. Beussink, J. N. Quiring, N. Fitzgerald, H. E. Greenberg, and S. A. Waldman The Pharmacokinetics of Nebulized Nanocrystal Budesonide Suspension in Healthy Volunteers J. Clin. Pharmacol., January 1, 2004; 44(1): 67 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Miller-Larsson, A. R&D, O. Selroos, D. R. Dorscheid, and S. R. White No Evidence of Glucocorticosteroid-induced Apoptosis of Airway Epithelial Cells In Vivo Am. J. Respir. Crit. Care Med., June 1, 2002; 165(11): 1567 - 1568. [Full Text]
|
|
|
|
|
|
M. Jendbro, C.-J. Johansson, P. Strandberg, H. Falk-Nilsson, and S. Edsbäcker Pharmacokinetics of Budesonide and Its Major Ester Metabolite after Inhalation and Intravenous Administration of Budesonide in the Rat Drug Metab. Dispos., April 13, 2001; 29(5): 769 - 776. [Abstract] [Full Text]
|
|
|
|
 |
|
 L. Xu, R. Olivenstein, J. G. Martin, and W. S. Powell Inhaled budesonide inhibits OVA-induced airway narrowing, inflammation, and cys-LT synthesis in BN rats J Appl Physiol, November 1, 2000; 89(5): 1852 - 1858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. MILLER-LARSSON, P. JANSSON, A. RUNSTROM, and R. BRATTSAND Prolonged Airway Activity and Improved Selectivity of Budesonide Possibly Due to Esterification Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): 1455 - 1461. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
