Comparative toxicity and toxicokinetic studies of oxiracetam and (S)-oxiracetam in dogs.

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.

[Bioassay for enrich-blood bioactivity of Agelicae Sinensis Radix].

Danggui, Agelicae Sinensis Radix, is a widely used Chinese herb to enrich blood, but its quality cannot be effectively assessed by the known chemical markers such as ferulic acid, ligustilide, polysaccharides, etc. A new bioassay was therefore developed to quantify the Enrich-Blood Bioactivity (EBB) for the quality assessment of Danggui raw materials. Danggui sample was first extracted with ethanol and water, respectively. Then the ethanolic extract and water extract were mixed as a test sample to quantify the amount of EBB by mice experiment. The blood deficiency mode in mice was developed by intraperitoneal injecting cyclophospharmide and phenylhdrazine hydrochloride. The quantity of red blood cell was chosen as EBB marker. Cyclosporine A was chosen as a control substance. EBB in analytes was quantified by the amount reaction of parallel line analysis (3, 3') method. The results indicated that the reliability test for quantifying EBB was passed through and the measured value was valid. The analytes showed the significant EBB (P < 0.05). The correlation coefficient was 0.9984 (n=5) between the amount of cyclosporine A (0.035-0.56 g x kg(-1)) and the increased number of red blood cell. The relative standard deviation (RSY) on the amount of EBB was estimated to be 6.15% (n = 6) by six replicated tests, and the confidence limit rate was 26.68% (n = 6). Five Danggui samples, which were collected from different cultivation areas with various morphological characters, showed the variety of EBB in the range of 21.95-44.16 U x g(-1). It is concluded that the developed method is accurate to quantify the EBB of Danggui raw materials, and is therefore suitable to assess its quality.