title: SULT 1A3 single-nucleotide polymorphism and the single dose pharmacokinetics of inhaled salbutamol enantiomers: are some athletes at risk of higher urine levels?
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.
authors.affiliation: School of Pharmacy, University of Tasmania, Hobart, TAS, 7001, Australia.
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Jacobson
authors.forename: Kwang Choon
authors.initials: KC
authors.lastname: Yee
authors.forename: Richard
authors.initials: R
authors.lastname: Wood-Baker
authors.forename: E Haydn
authors.initials: EH
authors.lastname: Walters
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry; D015239:Arylsulfotransferase / Q000235:genetics*; D001249:Asthma / Q000188:drug therapy; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry; D002853:Chromatography, Liquid; D016903:Drug Monitoring; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; D015239:Arylsulfotransferase; C403170:monoamine-sulfating phenol sulfotransferase; D000420:Albuterol
keywords: albuterol; metabolism; pharmacogenetics; sports doping