@article{oai:kanazawa-u.repo.nii.ac.jp:00014983,
 author = {崔, 吉道 and 宮本, 謙一 and Hirosawa, Iori and Ishikawa, Mai and Ogino, Mio and Ito, Hiroshi and Hirao, Takuya and Yamada, Harumi and Asahi, Mariko and Kotaki, Hajime and Sai, Yoshimichi and Miyamoto, Ken-ichi},
 issue = {4},
 journal = {Biopharmaceutics and Drug Disposition},
 month = {May},
 note = {Clenbuterol is a long-acting β2-adrenoceptor agonist and bronchodilator that is used for the treatment of asthma, but the desired activities reside almost exclusively in the (-)-R-enantiomer. This study examined enantioselectivity in the disposition of clenbuterol following administration of clenbuterol racemate to rats. Concentrations of clenbuterol enantiomers in plasma, urine and bile were determined by LC-MS/MS assay with a Chirobiotic T column. This method was confirmed to show high sensitivity, specificity and precision, and clenbuterol enantiomers in 0.1ml volumes of plasma were precisely quantified at concentrations as low as 0.25ng/ml. The pharmacokinetic profiles of clenbuterol enantiomers following intravenous and intraduodenal administration of clenbuterol racemate (2mg/kg) in rats were significantly different. The distribution volume of (-)-R-clenbuterol (9.17l/kg) was significantly higher than that of (+)-S-clenbuterol (4.14l/kg). The total body clearance of (-)-R-clenbuterol (13.5ml/min/kg) was significantly higher than that of the (+)-S-enantiomer (11.5ml/min/kg). An in situ absorption study in jejunal loops showed no difference in the residual amount between the (-)-R- and (+)-S-enantiomers. Urinary clearance was the same for the two enantiomers, but biliary excretion of (-)-R-clenbuterol was higher than that of the (+)-S-enantiomer. The fractions of free (non-protein-bound) (-)-R- and (+)-S-clenbuterol in rat plasma were 48.8% and 33.1%, respectively. These results indicated that there are differences in the distribution and excretion of the clenbuterol enantiomers, and these may be predominantly due to enantioselective protein binding. © 2013 John Wiley & Sons, Ltd., 発行後1年より全文公開},
 pages = {207--217},
 title = {Enantioselective disposition of clenbuterol in rats},
 volume = {35},
 year = {2014}
}