Acta Pharm. 66 (2016) 279-287

 

full paper

Original research paper

 

Pharmacokinetic comparisons of S-oxiracetam and R-oxiracetam in beagle dogs

WUSAN WANG, HUI JI, TINGTING LI, YUANWEI JIA and HAITANG XIE

cpujihui@sina.com; dreamerltt@163.com

1 Department of Pharmacology, College of Pharmacy, China Pharmaceutical University, Nanjing 210000, China

2 Yijishan Hospital, Wannan Medical College,Wuhu 241002, Anhui Province, China

Accepted October 27, 2015

Published online March 24, 2016

 

A pharmacokinetic comparison and conformational stability study of S-oxiracetam (S-ORT) and R-oxiracetam (R-ORT) in beagle dogs was used to investigate the possible mechanism of different effects of two oxiracetam enantiomers through a random crossover design. After drug administration to beagle dogs, blood samples were collected at different time points for pharmacokinetic analysis using the UPLC-ESI-MS/MS method. Parts of plasma samples were used for conformation transformation studies using a normal phase high performance liquid chromatographic (NP HPLC) method. The study showed that oxiracetam enantiomers maintained their original conformation when administered orally to beagle dogs. Concentrations of S-ORT were significantly higher than R-ORT 1.5 and 2 h after administration; the AUC0-∞ of S-ORT after oral administration tended to be higher than that of R-ORT, which showed that the different effects between S-ORT and R-ORT may be partly associated with their distinctive absorption at least.

 

Keywords: S-oxiracetam, R-oxiracetam, conformation, pharmacokinetics, beagle dogs