Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: A randomised crossover studyCitation formats

  • Authors:
  • Martin H. Brutsche
  • Ingrid Carlen Brutsche
  • Mohamed Munavvar
  • Stephen J. Langley
  • Catherine M. Masterson
  • And 4 others
  • External authors:
  • Peter T. Daley-Yates
  • Ronan Brown
  • Adnan Custovic
  • Ashley Woodcock

Standard

Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: A randomised crossover study. / Brutsche, Martin H.; Brutsche, Ingrid Carlen; Munavvar, Mohamed; Langley, Stephen J.; Masterson, Catherine M.; Daley-Yates, Peter T.; Brown, Ronan; Custovic, Adnan; Woodcock, Ashley.

In: The Lancet, Vol. 356, No. 9229, 12.08.2000, p. 556-561.

Research output: Contribution to journalArticle

Harvard

Brutsche, MH, Brutsche, IC, Munavvar, M, Langley, SJ, Masterson, CM, Daley-Yates, PT, Brown, R, Custovic, A & Woodcock, A 2000, 'Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: A randomised crossover study' The Lancet, vol. 356, no. 9229, pp. 556-561.

APA

Brutsche, M. H., Brutsche, I. C., Munavvar, M., Langley, S. J., Masterson, C. M., Daley-Yates, P. T., ... Woodcock, A. (2000). Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: A randomised crossover study. The Lancet, 356(9229), 556-561.

Vancouver

Brutsche MH, Brutsche IC, Munavvar M, Langley SJ, Masterson CM, Daley-Yates PT et al. Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: A randomised crossover study. The Lancet. 2000 Aug 12;356(9229):556-561.

Author

Brutsche, Martin H. ; Brutsche, Ingrid Carlen ; Munavvar, Mohamed ; Langley, Stephen J. ; Masterson, Catherine M. ; Daley-Yates, Peter T. ; Brown, Ronan ; Custovic, Adnan ; Woodcock, Ashley. / Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: A randomised crossover study. In: The Lancet. 2000 ; Vol. 356, No. 9229. pp. 556-561.

Bibtex

@article{f0c0440378544274a2468148df54070d,
title = "Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: A randomised crossover study",
abstract = "Background. Inhaled corticosteroids are currently the cornerstone of asthma treatment. Some studies of high-dose fluticasone propionate in patients with no or mild asthma have, however, suggested substantial systemic absorption. We investigated the pharmacokinetics of fluticasone propionate in patients with asthma receiving appropriate doses for severity. Methods. We did a double-blind, randomised, crossover study in 11 patients with asthma and 13 matched healthy controls (age 20-65 years; asthma patients forced expiratory volume in 1 s <75{\%} and stable on high-dose inhaled corticosteroids). Patients received one 1000 μg intravenous dose or 1000 μg daily for 7 days inhaled (via spacer device) fluticasone propionate. In the 12 h after dosing, we monitored plasma fluticasone propionate and cortisol concentrations by mass spectrometry and competitive immunoassay with use of direct chemiluminescence. Analysis was by intention to treat. Findings. After inhalation, geometric mean values were significantly lower in the asthma group than in controls for fluticasone propionate plasma area under curve (1082 [95{\%} CI 850-1451] vs 2815 pg mL-1 h-1 [2262-3949], -62{\%} difference [45-72]; p <0.001), maximum concentrations (117 [91-159] vs 383 pg/mL [302-546], -68{\%} [-50 to -81]; p <0.001), and systemic bioavailability (10.1 [7.9-14.0] vs 21.4{\%} [15.4-32.2], -54{\%} [-27 to -70]; p = 0.001). Intravenous-dose clearance, volume of distribution at steady state, plasma half-life, and mean residence time, were similar in the two groups. Less suppression of plasma cortisol concentrations was seen in the asthma group than in controls 4-12 h after inhaled fluticasone propionate. Interpretation. Systemic availability of fluticasone propionate is substantially less in patients with moderate to severe asthma than in healthy controls. Inhaled corticosteroids that are absorbed through the lungs need to be assessed in patients who are receiving doses appropriate for disease severity, and not in normal volunteers.",
keywords = "Administration, Inhalation, Administration, Topical, Adult, Aged, administration & dosage: Androstadienes, administration & dosage: Anti-Asthmatic Agents, administration & dosage: Anti-Inflammatory Agents, Area Under Curve, drug therapy: Asthma, Biological Availability, Comparative Study, Cross-Over Studies, Double-Blind Method, Female, Humans, metabolism: Hydrocortisone, Male, Middle Aged, Research Support, Non-U.S. Gov't, drug effects: Respiratory Mechanics",
author = "Brutsche, {Martin H.} and Brutsche, {Ingrid Carlen} and Mohamed Munavvar and Langley, {Stephen J.} and Masterson, {Catherine M.} and Daley-Yates, {Peter T.} and Ronan Brown and Adnan Custovic and Ashley Woodcock",
year = "2000",
month = "8",
day = "12",
language = "English",
volume = "356",
pages = "556--561",
journal = "The Lancet",
issn = "0140-6736",
publisher = "The Lancet Publishing Group",
number = "9229",

}

RIS

TY - JOUR

T1 - Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: A randomised crossover study

AU - Brutsche, Martin H.

AU - Brutsche, Ingrid Carlen

AU - Munavvar, Mohamed

AU - Langley, Stephen J.

AU - Masterson, Catherine M.

AU - Daley-Yates, Peter T.

AU - Brown, Ronan

AU - Custovic, Adnan

AU - Woodcock, Ashley

PY - 2000/8/12

Y1 - 2000/8/12

N2 - Background. Inhaled corticosteroids are currently the cornerstone of asthma treatment. Some studies of high-dose fluticasone propionate in patients with no or mild asthma have, however, suggested substantial systemic absorption. We investigated the pharmacokinetics of fluticasone propionate in patients with asthma receiving appropriate doses for severity. Methods. We did a double-blind, randomised, crossover study in 11 patients with asthma and 13 matched healthy controls (age 20-65 years; asthma patients forced expiratory volume in 1 s <75% and stable on high-dose inhaled corticosteroids). Patients received one 1000 μg intravenous dose or 1000 μg daily for 7 days inhaled (via spacer device) fluticasone propionate. In the 12 h after dosing, we monitored plasma fluticasone propionate and cortisol concentrations by mass spectrometry and competitive immunoassay with use of direct chemiluminescence. Analysis was by intention to treat. Findings. After inhalation, geometric mean values were significantly lower in the asthma group than in controls for fluticasone propionate plasma area under curve (1082 [95% CI 850-1451] vs 2815 pg mL-1 h-1 [2262-3949], -62% difference [45-72]; p <0.001), maximum concentrations (117 [91-159] vs 383 pg/mL [302-546], -68% [-50 to -81]; p <0.001), and systemic bioavailability (10.1 [7.9-14.0] vs 21.4% [15.4-32.2], -54% [-27 to -70]; p = 0.001). Intravenous-dose clearance, volume of distribution at steady state, plasma half-life, and mean residence time, were similar in the two groups. Less suppression of plasma cortisol concentrations was seen in the asthma group than in controls 4-12 h after inhaled fluticasone propionate. Interpretation. Systemic availability of fluticasone propionate is substantially less in patients with moderate to severe asthma than in healthy controls. Inhaled corticosteroids that are absorbed through the lungs need to be assessed in patients who are receiving doses appropriate for disease severity, and not in normal volunteers.

AB - Background. Inhaled corticosteroids are currently the cornerstone of asthma treatment. Some studies of high-dose fluticasone propionate in patients with no or mild asthma have, however, suggested substantial systemic absorption. We investigated the pharmacokinetics of fluticasone propionate in patients with asthma receiving appropriate doses for severity. Methods. We did a double-blind, randomised, crossover study in 11 patients with asthma and 13 matched healthy controls (age 20-65 years; asthma patients forced expiratory volume in 1 s <75% and stable on high-dose inhaled corticosteroids). Patients received one 1000 μg intravenous dose or 1000 μg daily for 7 days inhaled (via spacer device) fluticasone propionate. In the 12 h after dosing, we monitored plasma fluticasone propionate and cortisol concentrations by mass spectrometry and competitive immunoassay with use of direct chemiluminescence. Analysis was by intention to treat. Findings. After inhalation, geometric mean values were significantly lower in the asthma group than in controls for fluticasone propionate plasma area under curve (1082 [95% CI 850-1451] vs 2815 pg mL-1 h-1 [2262-3949], -62% difference [45-72]; p <0.001), maximum concentrations (117 [91-159] vs 383 pg/mL [302-546], -68% [-50 to -81]; p <0.001), and systemic bioavailability (10.1 [7.9-14.0] vs 21.4% [15.4-32.2], -54% [-27 to -70]; p = 0.001). Intravenous-dose clearance, volume of distribution at steady state, plasma half-life, and mean residence time, were similar in the two groups. Less suppression of plasma cortisol concentrations was seen in the asthma group than in controls 4-12 h after inhaled fluticasone propionate. Interpretation. Systemic availability of fluticasone propionate is substantially less in patients with moderate to severe asthma than in healthy controls. Inhaled corticosteroids that are absorbed through the lungs need to be assessed in patients who are receiving doses appropriate for disease severity, and not in normal volunteers.

KW - Administration, Inhalation

KW - Administration, Topical

KW - Adult

KW - Aged

KW - administration & dosage: Androstadienes

KW - administration & dosage: Anti-Asthmatic Agents

KW - administration & dosage: Anti-Inflammatory Agents

KW - Area Under Curve

KW - drug therapy: Asthma

KW - Biological Availability

KW - Comparative Study

KW - Cross-Over Studies

KW - Double-Blind Method

KW - Female

KW - Humans

KW - metabolism: Hydrocortisone

KW - Male

KW - Middle Aged

KW - Research Support, Non-U.S. Gov't

KW - drug effects: Respiratory Mechanics

M3 - Article

VL - 356

SP - 556

EP - 561

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9229

ER -