Rapid onset of tolerance to the bronchoprotective effect of salmeterol

R. Bhagat, Sanjay Kalra, V. A. Swystun, D. W. Cockcroft

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

Introduction: Twice-daily inhaled salmeterol for 4 weeks produces marked reduction in its acute bronchoprotective effect against methacholine. This investigation examined the onset of this effect over 5 days, and also assessed cross-tolerance with salbutamol. Subjects and methods: Ten asthmatic volunteers who were able to withhold β2-agonist therapy for 4 weeks before and during the study participated in a double-blind, crossover, placebo- controlled study with two random-order treatment periods: inhaled salmeterol, 50 μg twice a day for seven doses, and placebo in similar fashion. Methacholine inhalation tests were done 1 h after doses 1, 3, 5, and 7, and then 24 h after the last dose of the study inhaler 10 minutes after 200 μg of salbutamol. Results: Baseline FEV1 value before doses 3, 5, and 7 of salmeterol (ie, 12 b after salmeterol) was significantly higher than all other (n=7) values. Twenty-four hours after the last dose of salmeterol, the FEV1 was no different from that during the placebo period. The geometric mean methacholine concentration causing a 20% fall in FEV1 (PC20) after the first dose of salmeterol (6.1 mg/mL) was statistically similar to the value achieved 10 in after salbutamol after the placebo period (8.3 mg/mL), and these were significantly (analysis of variance, p<0.00005) larger than the second, third, and fourth salmeterol days (3.4 mg/mL, 2.6 mg/mL, 1,9 mg/mL, respectively). The methacholine PC20 10 min after salbutamol measured after the salmeterol period was significantly lower than after placebo (2.3 mg/mL vs 8.3 mg/mL; p<0.001). Conclusions: Tolerance to the acute bronchoprotective effect of salmeterol was significant after the first two doses and progressively increased to the seventh dose. Tolerance to the acute bronchoprotective effect of salbutamol was significant after regular use of salmeterol for seven doses.

Original languageEnglish (US)
Pages (from-to)1235-1239
Number of pages5
JournalChest
Volume108
Issue number5
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Albuterol
Methacholine Chloride
Placebos
Salmeterol Xinafoate
Nebulizers and Vaporizers
Inhalation
Volunteers
Analysis of Variance
Therapeutics

Keywords

  • airway hyperresponsiveness
  • asthma
  • bronchoprotection
  • methacholine
  • salmeterol

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Rapid onset of tolerance to the bronchoprotective effect of salmeterol. / Bhagat, R.; Kalra, Sanjay; Swystun, V. A.; Cockcroft, D. W.

In: Chest, Vol. 108, No. 5, 01.01.1995, p. 1235-1239.

Research output: Contribution to journalArticle

Bhagat, R. ; Kalra, Sanjay ; Swystun, V. A. ; Cockcroft, D. W. / Rapid onset of tolerance to the bronchoprotective effect of salmeterol. In: Chest. 1995 ; Vol. 108, No. 5. pp. 1235-1239.
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abstract = "Introduction: Twice-daily inhaled salmeterol for 4 weeks produces marked reduction in its acute bronchoprotective effect against methacholine. This investigation examined the onset of this effect over 5 days, and also assessed cross-tolerance with salbutamol. Subjects and methods: Ten asthmatic volunteers who were able to withhold β2-agonist therapy for 4 weeks before and during the study participated in a double-blind, crossover, placebo- controlled study with two random-order treatment periods: inhaled salmeterol, 50 μg twice a day for seven doses, and placebo in similar fashion. Methacholine inhalation tests were done 1 h after doses 1, 3, 5, and 7, and then 24 h after the last dose of the study inhaler 10 minutes after 200 μg of salbutamol. Results: Baseline FEV1 value before doses 3, 5, and 7 of salmeterol (ie, 12 b after salmeterol) was significantly higher than all other (n=7) values. Twenty-four hours after the last dose of salmeterol, the FEV1 was no different from that during the placebo period. The geometric mean methacholine concentration causing a 20{\%} fall in FEV1 (PC20) after the first dose of salmeterol (6.1 mg/mL) was statistically similar to the value achieved 10 in after salbutamol after the placebo period (8.3 mg/mL), and these were significantly (analysis of variance, p<0.00005) larger than the second, third, and fourth salmeterol days (3.4 mg/mL, 2.6 mg/mL, 1,9 mg/mL, respectively). The methacholine PC20 10 min after salbutamol measured after the salmeterol period was significantly lower than after placebo (2.3 mg/mL vs 8.3 mg/mL; p<0.001). Conclusions: Tolerance to the acute bronchoprotective effect of salmeterol was significant after the first two doses and progressively increased to the seventh dose. Tolerance to the acute bronchoprotective effect of salbutamol was significant after regular use of salmeterol for seven doses.",
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N2 - Introduction: Twice-daily inhaled salmeterol for 4 weeks produces marked reduction in its acute bronchoprotective effect against methacholine. This investigation examined the onset of this effect over 5 days, and also assessed cross-tolerance with salbutamol. Subjects and methods: Ten asthmatic volunteers who were able to withhold β2-agonist therapy for 4 weeks before and during the study participated in a double-blind, crossover, placebo- controlled study with two random-order treatment periods: inhaled salmeterol, 50 μg twice a day for seven doses, and placebo in similar fashion. Methacholine inhalation tests were done 1 h after doses 1, 3, 5, and 7, and then 24 h after the last dose of the study inhaler 10 minutes after 200 μg of salbutamol. Results: Baseline FEV1 value before doses 3, 5, and 7 of salmeterol (ie, 12 b after salmeterol) was significantly higher than all other (n=7) values. Twenty-four hours after the last dose of salmeterol, the FEV1 was no different from that during the placebo period. The geometric mean methacholine concentration causing a 20% fall in FEV1 (PC20) after the first dose of salmeterol (6.1 mg/mL) was statistically similar to the value achieved 10 in after salbutamol after the placebo period (8.3 mg/mL), and these were significantly (analysis of variance, p<0.00005) larger than the second, third, and fourth salmeterol days (3.4 mg/mL, 2.6 mg/mL, 1,9 mg/mL, respectively). The methacholine PC20 10 min after salbutamol measured after the salmeterol period was significantly lower than after placebo (2.3 mg/mL vs 8.3 mg/mL; p<0.001). Conclusions: Tolerance to the acute bronchoprotective effect of salmeterol was significant after the first two doses and progressively increased to the seventh dose. Tolerance to the acute bronchoprotective effect of salbutamol was significant after regular use of salmeterol for seven doses.

AB - Introduction: Twice-daily inhaled salmeterol for 4 weeks produces marked reduction in its acute bronchoprotective effect against methacholine. This investigation examined the onset of this effect over 5 days, and also assessed cross-tolerance with salbutamol. Subjects and methods: Ten asthmatic volunteers who were able to withhold β2-agonist therapy for 4 weeks before and during the study participated in a double-blind, crossover, placebo- controlled study with two random-order treatment periods: inhaled salmeterol, 50 μg twice a day for seven doses, and placebo in similar fashion. Methacholine inhalation tests were done 1 h after doses 1, 3, 5, and 7, and then 24 h after the last dose of the study inhaler 10 minutes after 200 μg of salbutamol. Results: Baseline FEV1 value before doses 3, 5, and 7 of salmeterol (ie, 12 b after salmeterol) was significantly higher than all other (n=7) values. Twenty-four hours after the last dose of salmeterol, the FEV1 was no different from that during the placebo period. The geometric mean methacholine concentration causing a 20% fall in FEV1 (PC20) after the first dose of salmeterol (6.1 mg/mL) was statistically similar to the value achieved 10 in after salbutamol after the placebo period (8.3 mg/mL), and these were significantly (analysis of variance, p<0.00005) larger than the second, third, and fourth salmeterol days (3.4 mg/mL, 2.6 mg/mL, 1,9 mg/mL, respectively). The methacholine PC20 10 min after salbutamol measured after the salmeterol period was significantly lower than after placebo (2.3 mg/mL vs 8.3 mg/mL; p<0.001). Conclusions: Tolerance to the acute bronchoprotective effect of salmeterol was significant after the first two doses and progressively increased to the seventh dose. Tolerance to the acute bronchoprotective effect of salbutamol was significant after regular use of salmeterol for seven doses.

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