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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?
journal contributionposted on 2023-05-17, 23:36 authored by Glenn JacobsonGlenn Jacobson, Kwang YeeKwang Yee, Wood-Baker, R, Eugene WaltersEugene Walters
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.
Publication titleDrug testing and analysis
Department/SchoolSchool of Pharmacy and Pharmacology
PublisherJohn Wiley & Sons Ltd.
Place of publicationUK
Rights statementCopyright 2014 John Wiley & Sons