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SULT 1A3 single-nucleotide polymorphism and the single dose pharmacokinetics of inhaled salbutamol enantiomers: Are some athletes at risk of higher urine levels?
Citation
Jacobson, GA and Yee, KC and Wood-Baker, R and Walters, EH, SULT 1A3 single-nucleotide polymorphism and the single dose pharmacokinetics of inhaled salbutamol enantiomers: Are some athletes at risk of higher urine levels?, Drug testing and analysis, 7 Article 1645. ISSN 1942-7611 (2015) [Refereed Article]
Copyright Statement
Copyright 2014 John Wiley & Sons
DOI: doi:10.1002/dta.1645
Abstract
The study was designed to investigate the effect of a common genetic variation of the main salbutamol metabolizing enzyme SULT1A3 (single nucleotide polymorphism 105A > G, rs1975350) on the stereoselective pharmacokinetics of salbutamol. Subjects were administered a 400 µg dose of inhaled salbutamol via a large volume spacer and blood samples were collected over 4 h. Plasma levels of (R)- and (S)-salbutamol were determined by an enantioselective liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. Twenty-five subjects with asthma were recruited and underwent SULT1A3 genotyping, from which four SNP homozygote (GG) subjects and nine wild-type (AA) subjects were selected to participated in the pharmacokinetic investigation. There were no differences in pharmacokinetic parameters (t1/2, Cmax, AUC0-4h) between SNP and wild-type genotypes for either the R- or S-enantiomer. Observed Cmax of R- and S-salbutamol [mean (SD)] was 0.64 (0.30) ng/mL and 1.32 (0.98) ng/mL, respectively. The mean t1/2 of R- and S-salbutamol was estimated at 2.94 (1.17) h and 7.86 (6.14) h respectively. The AUC0-4h of R- and S-salbutamol was 14.0 (6.8) and 38.3 (19.5) ng/mL.h respectively. In conclusion, the common SULT1A3 SNP 105A > G is not an important determinant of salbutamol enantiomer pharmacokinetics under normal clinical use and does not place some individuals at greater risk of accumulation in the body.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | enantiomer, salbutamo, albuterol, metabolism, pharmacogenetics, sports doping |
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Pharmacology and pharmaceutical sciences |
| Research Field: | Pharmaceutical sciences |
| Objective Division: | Health |
| Objective Group: | Other health |
| Objective Field: | Other health not elsewhere classified |
| UTAS Author: | Jacobson, GA (Professor Glenn Jacobson) |
| UTAS Author: | Yee, KC (Dr Kwang Yee) |
| UTAS Author: | Wood-Baker, R (Professor Richard Wood-Baker) |
| UTAS Author: | Walters, EH (Professor Haydn Walters) |
| ID Code: | 90374 |
| Year Published: | 2015 (online first 2014) |
| Web of Science® Times Cited: | 21 |
| Deposited By: | Pharmacy |
| Deposited On: | 2014-04-02 |
| Last Modified: | 2017-11-02 |
| Downloads: | 0 |
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