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

机译:S-奥拉西坦和R-奥拉西坦在比格犬中的药代动力学比较

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摘要

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.
机译:使用比格犬的S-奥拉西坦(S-ORT)和R-奥拉西坦(R-ORT)进行药代动力学比较和构象稳定性研究,通过随机交叉设计研究两种奥拉西坦对映体不同作用的可能机制。向比格犬给药后,在不同时间点采集血样,使用UPLC-ESI-MS / MS方法进行药代动力学分析。使用正相高效液相色谱(NP HPLC)方法将部分血浆样品用于构象转化研究。研究表明,对比格犬口服时,奥拉西坦对映体保持其原始构象。给药后1.5小时和2小时,S-ORT的浓度显着高于R-ORT。口服后S-ORT的AUC0-∞倾向于高于R-ORT,这表明S-ORT和R-ORT之间的不同作用至少部分与其独特的吸收有关。

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