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Research in Pharmacy |
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Salbutamol (b-agonist therapy)
| Salbutamol is a first-line
drug used in treatment of acute asthma exacerbations. This research
revolves around the chiral nature of salbutamol (which is delivered
as a 1:1 mixture of (R) and (S)-salbutamol). It is generally
considered that the (S)-salbutamol enantiomer is inactive, however,
there is some evidence to suggest that (S)-salbutamol may actually
worsen asthma symptoms and (S)-salbutamol accumulates relative
to (R)-salbutamol due to slower metabolism. Adding further complexity,
there are several common genetic differences at the drug receptor
level in patients (SNPs; single nucleotide polymorphisms) |
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Both pharmacogenetic
determinants of response (drug receptor and metabolism enzyme
SNPs) have not previously been studied with regard to both (R)
and (S) enantiomers of salbutamol which is the focus of current
research. A publication arising from this project was the first
to report plasma levels of (R) and (S)-salbutamol in acute severe
asthmatics. Ongoing work has shown that in some acute severe
patients, alarmingly over 80% of salbutamol in plasma is the
inactive (S)-salbutamol. Further genetic based projects are
underway. |
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Selected
publications:
Jacobson GA, Chong FV, Wood-Baker R. (R,S)-Salbutamol plasma
concentrations in severe asthma. J Clin Pharm Ther. 2003 Jun;28(3):235-8.
Jacobson GA, Chong FV, Davies NW. LC-MS method for the determination
of albuterol enantiomers in human plasma using manual solid-phase
extraction and a non-deuterated internal standard. J Pharm
Biomed Anal. 2003 Apr 10;31(6):1237-43. |
| which appear to have significant
clinical outcomes. Furthermore, there is recent evidence that
there are common SNPs of the enzyme SULT1A3 involved in metabolism. |
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For further information see Glenn
Jacobson
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