Am. J. Respir. Crit. Care Med., Volume 160, Number 4, October 1999, 1238-1243

Therapeutic Equivalence of Spiros Dry Powder Inhaler and Ventolin Metered Dose Inhaler
A Bioassay Using Methacholine

RICHARD C. AHRENS, LESLIE HENDELES, WILLIAM R. CLARKE, ROBERT J. DOCKHORN, MALCOLM R. HILL, LEIGH M. VAUGHAN, CHERI LUX, and SEUNG-HO HAN

College of Medicine, University of Iowa, Iowa City, Iowa; College of Pharmacy, University of Florida, Gainesville, Florida; International Medical Technical Consultants, Inc., Lenexa, Kansas; and Clinical Development, Dura Pharmaceuticals, Inc., San Diego, California

Because chlorofluorocarbons (CFCs) contribute to depletion of stratospheric ozone, CFC-containing metered-dose inhalers (MDIs) such as Ventolin and Proventil are being phased out of production. In terms of delivery of albuterol to the lungs, we compared an alternative delivery system, the Spiros dry-powder inhaler (DPI), with Ventolin, using a methacholine challenge-based clinical bioassay. Twenty-four adults and adolescents with asthma completed this double-blind, four-period crossover study. Doses evaluated were one and three actuations each of Spiros and Ventolin (90- and 270-µg albuterol base). A methacholine challenge (Cockcroft method) was initiated 3 h before and 0.25 h after albuterol. Predose PC₂₀FEV₁ values were not significantly different between study days. Postdose PC₂₀FEV₁ results met standard bioassay study validity criteria: i.e., a significant dose-response relationship was present (p = 0.0002); tests for deviation from parallelism and overlap of dose-response curves were nonsignificant (p = 0.08, 0.69). By using Finney 2-by-2 bioassay analysis, we estimate that each Spiros actuation delivers 1.12 times as much albuterol to the airways as one Ventolin actuation (90% confidence interval, 0.68 to 1.94). There were no significant differences in markers of systemic effects (vital signs, potassium, and blood glucose concentrations). We conclude that Spiros and Ventolin inhalers deliver comparable quantities of albuterol to the airways.

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