Beta2-agonist Enantiomer Clinical Pharmacology
About our research
Our research focuses on exploring the differences in pharmacodynamics and pharmacokinetics of asthma drugs in relation to treating respiratory disease, as well as their application to muscle performance and sports doping.
Common asthma drugs include beta2-agonists, which act as bronchodilators. These drugs are also used for chronic obstructive pulmonary disease (COPD) but have other beneficial effects in the body including on skeletal muscle, the heart, and fat. Most commonly, these drugs are administered as 1 : 1 racemic mixtures of enantiomers, non-superimposable mirror image molecules, akin to a right and left hand. The beneficial biological activities, known as pharmacodynamics, mostly reside in only one of the enantiomers. The time course of drug in the body, known as pharmacokinetics, also differs between these enantiomers.
Specialist fields and areas of investigation
We have developed and routinely use advanced bioanalytical techniques (latest generation UPLC-MS/MS with enantioselective chiral column assays) to detect the enantiomers of beta2-agonists in a variety of biological tissues, such as blood, urine, brain, fat, skeletal and cardiac muscle, allowing us to investigate the clinical pharmacology and pharmacokinetics of these drugs attributable to each enantiomer.
Major achievements or grants
Our group was the first to highlight enantioselective disposition of R-salbutamol in cardiac tissue and is the first in the word to directly measure beta2-agonist enantiomers in epithelial lining fluid and lung biopsy tissue to investigate lung disposition following inhalation. Our current studies utilise horse models of asthma with collaborators at Charles Sturt University; horses develop a naturally occurring asthma called RAO (recurrent airway obstruction or "heaves").
The group is also internationally recognised for work related to enantioselective beta2-agonist bioanalytical applications in the area of sports doping. We have recently been the recipient of two international competitively funded World Anti-Doping Agency (WADA) grants. These projects aim to improve detection of beta2-agonists using enantiomer ratios to discriminate between permitted and prohibited dosing of beta2-agonists, which are currently only permitted to a predetermined dosing threshold.
How does your group Transform Healthcare in Tasmania and around the globe?
An improved understanding of differential enantioselective pharmacology, toxicology and lung pharmacokinetics for long acting beta2-agonists is long overdue, as the US Food and Drug Administration has recently raised concerns regarding the safety of this class of drug. Safety issues could in part be due to administration of mixtures of enantiomers where the inactive enantiomer for the short acting beta2-agonist salbutamol been shown to increase bronchial hyperreactivity (airway twitchiness).
Furthermore, our work has significant potential to improve international sports doping control of beta2-agonists which are allowed in competition, but excessive use has demonstrated this class of drug to be performance enhancing.