To investigate the effects of time interval and cumulative dosage of repetitive mild cellular hypoxia on shape of neurodegeneration and neuroprotection in mice, population spike amplitude (PSA) was measured during hypoxia and posthypoxic recovery in hippocampal slices from untreated control and mice pretreatedin vivo with a single or repeatedly intraperitoneal injection of 3-nitropropionate (3-NP). Posthypoxic recovery of PSA was dose-dependent in single pretreated slices, with maximal recovery on pretreatment attained with 20 mg/kg 3-NP (82±32%,P<0.01). Upon 5 and 9 treatments with 20 mg/kg 3-NP (dosage interval 3 days), PSA recovered to 38±9) % with the difference being not significant vs control group and (72±45)% with the difference being significant (P<0.05 to control,P<0.05 to 5 treatments), respectively. In contrast, with 2 days time interval, recovery after 5 and 9 treatments was (30±25)% and (16±14)%, respectively (without significant difference from control). Continued neuroprotection was also observed upon increase of dosage interval to 4 and 5 days. It was suggested that repetitive chemical hypoxia is a model for neurodegenerative disease and continued neuroprotection depending on time interval between repetitive hypoxic episodes rather than cumulative dosage. At appropriate time intervals increased neuronal hypoxic tolerance could be induced with number of hypoxic episodes.
To study the bioequivalence of Clavulanate Potassium and Amoxicillin (1∶7) dispersible tablets, a randomized cross—over study was conducted in 18 healthy volunteers. A single oral dose of 1000 mg Clavulanate Potassium and Amoxicillin (1∶7) dispersible tablets (Tested formulation, T) or Augmentin syrup (Reference formulation, R). Concentrations in plasma were determined with high-performance liquid chromatography. The main paramaters of T were: for Clavulanate Potassium and Amoxicillin, Cmax: 2.46±1.11 μg/ml and 18.81±7.26 μg/ml, Tmax: 1.12±0.23h and 1.30±0.34h, ACU(0–6h): 5.18±2.24 μg·h/ml and 45.09±14.53 μg·h/ml, t1/2: 1.43±0.44 h and 1.09±0.22 h., respectively. The relative bioavailability of T to R were 96.5±19.2% and 98.4±26.1%, respectively. Statistical analysis showed that the two formulations were bioequivalent.