A cumulative dose study of levalbuterol and racemic albuterol administered by hydrofluoroalkane-134a metered-dose inhaler in asthmatic subjects.
BACKGROUND
The short-acting beta(2)-agonists levalbuterol and racemic albuterol are available for administration through a hydrofluoroalkane-134a (HFA) metered-dose inhaler (MDI).


OBJECTIVE
This study compared the short-term safety and efficacy of cumulative doses of levalbuterol HFA MDI and racemic albuterol HFA MDI in asthmatic subjects.


METHODS
This was a randomized, modified-blind, active-controlled, multicenter, 2-way crossover study. Subjects (n = 49) were randomized to 16 cumulative doses (1x, 2x, 4x, 8x, and 16x) of levalbuterol (45 microg per dose) or racemic albuterol (90 microg per dose) administered over a 2-hour period. After a 7-day washout period, subjects were crossed over to the other treatment. After each dose, safety outcomes and pulmonary function were assessed.


RESULTS
Heart rate and (R)-albuterol exposure increased for both racemic albuterol HFA and levalbuterol HFA. For cumulative doses of 8x or greater, racemic albuterol HFA treatment had greater increases in mean heart rate than levalbuterol HFA (least-squares mean [+/- SD] difference at the 8x dose was 2.8 beats/min [95% CI, 0.3-5.3] and at the 16x dose was 3.5 beats/min [95% CI, 0.6-6.4]). (R)-albuterol plasma levels ranged from 10% to 18% higher after racemic albuterol HFA MDI dosing versus after levalbuterol HFA MDI. FEV(1) improvements were similar for both treatments. The relative potencies of the 2 therapies, based on FEV(1), were similar (ratio, 1.1 [90% CI, 0.9-1.2]; Finney method).


CONCLUSIONS
In this study single-day cumulative dosing of asthmatic subjects with levalbuterol HFA MDI or racemic albuterol HFA MDI resulted in similar improvements in FEV(1) and tolerability. Plasma (R)-albuterol levels and mean heart rate were less with levalbuterol HFA MDI.
Tripp
Kenneth
K
Sepracor, Inc, Marlborough, MA 01752, USA.
McVicar
William K
WK
Nair
Parameswaran
P
Corren
Jonathan
J
Pleskow
Warren W
WW
Goodwin
Elizabeth
E
Baumgartner
Rudolf A
RA
Hanrahan
John P
JP
D000280:Administration, Inhalation; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D008297:Male; D036501:Metered Dose Inhalers; D013147:Spirometry; D005466:Fluorocarbons
D000318:Adrenergic beta-Agonists; D000420:Albuterol; D001993:Bronchodilator Agents; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons