Asthma, Rhinitis, Other Respiratory DiseasesThe therapeutic ratio of R-albuterol is comparable with that of RS-albuterol in asthmatic patients☆,☆☆
Section snippets
Methods
The study was approved by the Göteborg University Ethics Committee, and all patients gave their full written informed consent before entry into the study. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Trial Practice, and prior approval was obtained from the Swedish Medical Products Agency. The sponsor (GlaxoWellcome) monitored the study.
Pharmacodynamics
Both R- and RS-albuterol (6.25-3600 μg) produced significant and dose-dependent increases in FEV1 (Fig 1). All doses significantly improved FEV1 versus the effects of placebo. The dose-response curve did not consistently plateau at the higher doses of R- and RS-albuterol tested. At the highest doses of R- and RS-albuterol (ie, 1600 and
Discussion
This study, using a more than two-10log cumulative dose-response design, shows that R- and RS-albuterol have a 2:1 potency ratio for improvement in FEV1 in asthmatic patients and shows that S-albuterol is clinically inactive. Because the RS-albuterol mixture contains only 50% R-albuterol, it is clear that the clinical effect of albuterol resides with the R-enantiomer. Furthermore, the therapeutic ratios of R- and RS-albuterol are very similar, suggesting that the S-enantiomer of albuterol does
Acknowledgements
We thank Drs Karina Joyce and Stephen Pleasance (International Bioanalysis) and Dr Malcolm York (Clinical Pathology), Glaxo-Wellcome R&D Ltd, Ware, United Kingdom) for their bioanalytic support. We also thank Helen Törnqvist, Eva Karlgren, and Marianne Robertsson of the Lung Pharmacology Group, Göteborg University, Sweden, for their help with the clinical phase of the study.
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Supported by a grant from Glaxo Wellcome Research & Development Limited.
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Reprint requests: Jan Lötvall, MD, PhD, Department of Respiratory Medicine and Allergology, Göteborg University, S-413 45 Gothenburg, Sweden.