Pharmacokinetic comparisons of S-oxiracetam and R-oxiracetam in beagle dogs.
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.
Wusan
W
Wang
Hui
H
Ji
Tingting
T
Li
Yuanwei
Y
Jia
Haitang
H
Xie
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004285:Dogs; D005260:Female; D065569:Gastrointestinal Absorption; D006207:Half-Life; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D015233:Models, Statistical; D018697:Nootropic Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D011759:Pyrrolidines / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry
D018697:Nootropic Agents; D011759:Pyrrolidines; C040619:oxiracetam