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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?
Author(s) -
Jacobson Glenn A,
Yee Kwang Choon,
WoodBaker Richard,
Walters E. Haydn
Publication year - 2015
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.1645
Subject(s) - salbutamol , pharmacokinetics , pharmacology , chemistry , single nucleotide polymorphism , urine , cmax , chromatography , medicine , genotype , asthma , biochemistry , gene
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 (t 1/2 , C max , AUC 0‐4h ) between SNP and wild‐type genotypes for either the R ‐ or S ‐enantiomer. Observed C max of R ‐ and S ‐salbutamol [mean (SD)] was 0.64 (0.30) ng/mL and 1.32 (0.98) ng/mL, respectively. The mean t 1/2 of R ‐ and S ‐salbutamol was estimated at 2.94 (1.17) h and 7.86 (6.14) h respectively. The AUC 0‐4h 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. Copyright © 2014 John Wiley & Sons, Ltd.