title: Influence of dose and route of administration on the enantioselective pharmacokinetics of TJ0711 hydrochloride in rats.
abstract: The enantioselective pharmacokinetics of TJ0711 hydrochloride were studied in rats given different doses of rac-TJ0711 hydrochloride via intravenous and oral routes. R- and S-TJ0711 hydrochloride were both rapidly absorbed, and the average AUC0-∞ of R-TJ0711 hydrochloride was greater than that of S-TJ0711 hydrochloride after intragastric administration, with an R/S AUC ratio 1.11 and 1.35 for 30 and 50 mg/kg dose group, respectively. In contrast, the average AUC0-∞ of R-TJ0711 hydrochloride was smaller than that of S-TJ0711 hydrochloride after intravenous injection, with an R/S AUC ratio 0.57 and 0.73 for 10 and 20 mg/kg dose group, respectively. R-TJ0711 hydrochloride plasma half-lives were shorter than those of S-TJ0711 hydrochloride for all groups. AUC0-4h and Cmax between the two enantiomers were significantly different after oral administration of 50 mg/kg dose of the racemate, while no significant differences between the two enantiomers were found for all the pharmacokinetic parameters of the 30 mg/kg dose group. Significant differences between the two enantiomers were detected for nearly all the pharmacokinetic parameters after intravenous administration, except for the VZ of 20 mg/kg dose group. This study suggests that dose and route of administration will influence the enantioselectivity in the pharmacokinetics of TJ0711 hydrochloride in rats.
authors.affiliation: School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China; Department of Biotechnology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, People's Republic of China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Sun
authors.forename: Zhaoze
authors.initials: Z
authors.lastname: Fan
authors.forename: Lei
authors.initials: L
authors.lastname: Hu
authors.forename: Yiming
authors.initials: Y
authors.lastname: Ma
authors.forename: Luqin
authors.initials: L
authors.lastname: Si
authors.forename: Jun
authors.initials: J
authors.lastname: Qiu
authors.forename: Gao
authors.initials: G
authors.lastname: Li
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D015394:Molecular Structure; D050198:Phenoxypropanolamines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
chemical_list: C558139:1-(4-(2-methoxyethyl)phenoxy)-3-(((2-2-methoxyphenoxy)ethyl)amino)-2-propanol; D050198:Phenoxypropanolamines
keywords: TJ0711 hydrochloride; enantiomer; enantioselective; pharmacokinetics; rats