title: Comparative pharmacokinetics and bile transformation of R-enantiomer and racemic bambuterol after single-dose intravenous, oral administration in rats and beagle dogs.
abstract: This study was to compare pharmacokinetics and bile transformation of R-enantiomer bambuterol with its racemate. Pharmacokinetics of R-enantiomer was investigated after single-dose intravenous and three doses of oral administration to rats and beagle dogs. To compare the pharmacokinetics with racemic bambuterol, the same oral doses of racemic bambuterol were also administrated; the blood and bile samples were collected by cannulation. A validated LC-MS/MS method was used to assess the level of bambuterol in plasma and bile. After single intravenous administration, no significant differences were observed between the two drugs in pharmacokinetic data. After oral dosing of R-bambuterol, the AUCs of R-enantiomer presented linear correlation. After same oral dosing of R-enantiomer and its racemate, all the pharmacokinetic parameters were equivalent. However, the clearance and apparent distribution had different results due to species and administration route difference. The bile transformation of these two compounds was similar and implicated that liver transformation accounted for the major metabolism of them. The bioavailability of R-enantiomer and racemate were comparative and relatively high in beagle dogs. Thus, R-enantiomer had a comparative pharmacokinetic profile and bile transformation with racemic bambuterol in rats and beagle dogs. These findings provided references for further clinical study.
authors.affiliation: School of Bioscience and Biotechnology, South China University of Technology, Higher Education Mega Center, 382 Wai Huan Dong Road, Guangzhou, 510006, People's Republic of China. guansu@scut.edu.cn.
authors.forename: Su
authors.initials: S
authors.lastname: Guan
authors.affiliation: School of Bioscience and Biotechnology, South China University of Technology, Higher Education Mega Center, 382 Wai Huan Dong Road, Guangzhou, 510006, People's Republic of China.
authors.forename: Chun-Yun
authors.initials: CY
authors.lastname: Hu
authors.affiliation: School of Bioscience and Biotechnology, South China University of Technology, Higher Education Mega Center, 382 Wai Huan Dong Road, Guangzhou, 510006, People's Republic of China.
authors.forename: Meng-Ying
authors.initials: MY
authors.lastname: He
authors.affiliation: School of Bioscience and Biotechnology, South China University of Technology, Higher Education Mega Center, 382 Wai Huan Dong Road, Guangzhou, 510006, People's Republic of China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Yang
authors.affiliation: School of Bioscience and Biotechnology, South China University of Technology, Higher Education Mega Center, 382 Wai Huan Dong Road, Guangzhou, 510006, People's Republic of China.
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Tang
authors.affiliation: School of Bioscience and Biotechnology, South China University of Technology, Higher Education Mega Center, 382 Wai Huan Dong Road, Guangzhou, 510006, People's Republic of China.
authors.forename: Jie-di
authors.initials: JD
authors.lastname: Chen
authors.affiliation: School of Bioscience and Biotechnology, South China University of Technology, Higher Education Mega Center, 382 Wai Huan Dong Road, Guangzhou, 510006, People's Republic of China.
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Huang
authors.affiliation: School of Bioscience and Biotechnology, South China University of Technology, Higher Education Mega Center, 382 Wai Huan Dong Road, Guangzhou, 510006, People's Republic of China. eventan2@163.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D004285:Dogs; D005260:Female; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013237:Stereoisomerism; D013726:Terbutaline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D013726:Terbutaline; C047766:bambuterol
keywords: Bambuterol; Beagle dogs; Pharmacokinetics; R-enantiomer; Rats