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.

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