Detrimental effects on bronchoprotection starts after the 5th dose of albuterol, worsens after 7 doses

This study aimed to determine the course of onset of tolerance to the bronchoprotective effect of salbutamol against methacholine. It was designed as a randomized, double-blind, placebo-controlled trial and included 13 patients with mild asthma. Each treatment period consisted of 7 twice-daily doses (2 puffs of 100 μg of salbutamol or placebo). Methacholine challenges were conducted 24 hours apart on 4 consecutive days, 10 minutes after the first, third, fifth, and seventh doses.
A single dose of salbutamol shifted the methacholine PC20 approximately 5-fold from a geometric mean of 2.1 mg/mL to 10.7 mg/mL. Maximal bronchoprotection after the active treatment occurred on day 2 after the third dose. After the fifth dose the methacholine PC20 was trending downward, and on day 4 the bronchoprotective effect of salbutamol had significantly decreased from its peak protection.
The authors concluded that the detrimental effects on bronchoprotection after regular use of salbutamol manifest after 5 doses and are significantly reduced from peak protection after 7 doses.
Asthma Inhalers (click to enlarge the image).
References:
Salbutamol tolerance to bronchoprotection: course of onset. Sarah L. Stewart, BSc, Alexandra L. Martin, BSc, Beth E. Davis, BSc, PhD, Donald W. Cockcroft, BSc, MD, FRCP(C). Annals of Allergy, Asthma & Immunology, Volume 109, Issue 6 , Pages 454-457, December 2012.