Comparative toxicity and toxicokinetic studies of oxiracetam and (S)-oxiracetam in dogs |
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| Authors: | Tian-tian Liu Xin-miao Guo Zu-yuan Rong Xiang-feng Ye Jin-feng Wei Ai-ping Wang |
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| Affiliation: | 1. New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;2. Beijing Union-Genius Pharmaceutical Technology Co., LTD, Beijing, China;3. Sichuan Institute for Food and Drug Control, Sichuan, China;4. Beijing Union-Genius Pharmaceutical Technology Co., LTD, Beijing, China |
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| Abstract: | Oxiracetam (ORT) is known as a derivative of piracetam in the family of nootropics for treating memory impairment and cognition disorders. Given the chiral toxicological concerns surrounding ORT and the absence studies of (S)-ORT, the toxicity and toxicokinetics of (S)-ORT, and comparative toxicology of oxiracetam were systematically investigated in dogs following acute and 13-week repeated oral dosing. The animal toxicity mainly manifested as loose stools in both the acute and the 13-week studies. The no-observed-adverse-effect level is proposed to be 100?mg/kg. The 13-week toxicokinetics study indicated that, in the (S)-ORT group, the time to peak concentration was delayed, elimination half-life extended, and apparent volume of distribution increased compared with the ORT group. The clearance rate increased at low- and mid-doses, but decreased in the high-dose group and was accompanied by drug accumulation. Compared with the same dose of ORT, (S)-ORT had a lower clearance rate and longer elimination half-life.
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| Keywords: | Oxiracetam enantiomer chiral toxicity toxicokinetics |
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