The pharmacokinetics of oxiracetam and its degraded substance(4-hydroxy-2-oxo-1-pyrrolidine acetic acid,HOPAA)after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method.Three...The pharmacokinetics of oxiracetam and its degraded substance(4-hydroxy-2-oxo-1-pyrrolidine acetic acid,HOPAA)after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method.Three groups of rats after an overnight fasted received 10 g/kg(n=6)oxiracetam suspensions orally,and 2 g/kg(n=6)normal or degraded oxiracetam injections intravenously via a caudal tail vein,respectively.Before the pharmacokinetic experiment,a simple safety evaluation testwas conducted on the degraded oxiracetam injections containing 16.16% HOPAA in mice.There was no mortality by a single intravenous dose of 2 g/kg of degraded oxiracetam injections within twoweeks,demonstrating that HOPAA was non-toxic in mice.Following intravenous administration of the normal injections,the plasma concentration-time curves of oxiracetam and HOPAA both showed a rapid elimination phase.The values of t_(1/2)were 3.1±1.5 h for oxiracetamand 0.8±0.2 h for HOPAA,andthemean residencetimes(MRT)were 1.2±0.1h and 0.8±0.1h,respectively.Oxiracetam and HOPAA after intravenous administration of the degraded oxiracetam injections presented elimination patterns similar to those observed in the normal injections.Oral pharmacokinetic results showed that the Tmax was less than 1.5 h for the two analytes,and both had a longer t_(1/2) and MRT than those of intravenous administration.Contents of HOPAA in three groupswere calculated based on AUC_(0-t) values of the two analytes.The quantitative change of HOPAA in vivo was also evaluated by comparing the plasma concentrations of HOPAA and oxiracetamat the same time for every group.Additionally,the values of absolute bioavailability of oxiracetam were about 8.0%and 7.4%calculated by the normal or degraded oxiracetam injections,whichwere far less than the value of 75%reported in literature,indicating the necessity of further study.展开更多
OBJETTIVE: To observe the effects of Yinxingdamo Injection combined with oxiracetam capsule on cognitive function and neurological deficit in patients with acute cerebral infarction. METHODS: A total of 76 patients wi...OBJETTIVE: To observe the effects of Yinxingdamo Injection combined with oxiracetam capsule on cognitive function and neurological deficit in patients with acute cerebral infarction. METHODS: A total of 76 patients with acute cerebral infarction were randomly divided into observation group and control group, with 38 patients in each group. Patients in the control group were treated with conventional western medicine and oxiracetam capsules while patients in the observation group were given Yinxingdamo injection intravenous drip treatment on the basis of the same treatment. After 4 weeks of treatment, the cognitive function of the two groups before and after treatment was observed [Simple Intelligence Scale(MMSE Score), Montreal Cognitive Assessment Scale(MoCA Score)], Neurological Deficit [Chinese Stroke Scale(CSS Score), Daily Life Activity ability(ADL score)], free radical biochemical indicators [malondialdehyde(MDA), oxide dismutase(SOD)] changes, and statistical effects of two groups. RESULTS: After treatment, the total effective rate of the observation group was 92.1%, which was significantly higher than 73.7% of the control group(P < 0.05). The MMSE score and MoCA score of the two groups were significantly increased after treatment(P < 0.05), and the MMSE score and MoCA score inobservation group were significantly increased after treatment than the control group(P < 0.05). The CSS scores of the two groups were significantly decreased after treatment(P < 0.05), and the ADL scores were significantly increased(P < 0.05). The improvement of CSS score and ADL score in the observation group were significantly better than those in the control group(P < 0.05), and serum MDA levels were significantly decreased in both groups after treatment(P < 0.05), and SOD levels were significantly increased(P < 0.05), and the improvement of MDA and SOD levels in the observation group was significantly better than that in the control group group(P < 0.05). CONCLUSION: Yinxingdamo injection combined with oxiracetam capsule can effectively inhibit the oxygen free radical reaction injury in patients with acute cerebral infarction, and significantly improve the symptoms of cognitive dysfunction and neurological deficit in patients. Its curative effect is exact and worthy of clinical application.展开更多
基金This work was financially supported from the National Nature Science Foundation of China(No.81173009).
文摘The pharmacokinetics of oxiracetam and its degraded substance(4-hydroxy-2-oxo-1-pyrrolidine acetic acid,HOPAA)after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method.Three groups of rats after an overnight fasted received 10 g/kg(n=6)oxiracetam suspensions orally,and 2 g/kg(n=6)normal or degraded oxiracetam injections intravenously via a caudal tail vein,respectively.Before the pharmacokinetic experiment,a simple safety evaluation testwas conducted on the degraded oxiracetam injections containing 16.16% HOPAA in mice.There was no mortality by a single intravenous dose of 2 g/kg of degraded oxiracetam injections within twoweeks,demonstrating that HOPAA was non-toxic in mice.Following intravenous administration of the normal injections,the plasma concentration-time curves of oxiracetam and HOPAA both showed a rapid elimination phase.The values of t_(1/2)were 3.1±1.5 h for oxiracetamand 0.8±0.2 h for HOPAA,andthemean residencetimes(MRT)were 1.2±0.1h and 0.8±0.1h,respectively.Oxiracetam and HOPAA after intravenous administration of the degraded oxiracetam injections presented elimination patterns similar to those observed in the normal injections.Oral pharmacokinetic results showed that the Tmax was less than 1.5 h for the two analytes,and both had a longer t_(1/2) and MRT than those of intravenous administration.Contents of HOPAA in three groupswere calculated based on AUC_(0-t) values of the two analytes.The quantitative change of HOPAA in vivo was also evaluated by comparing the plasma concentrations of HOPAA and oxiracetamat the same time for every group.Additionally,the values of absolute bioavailability of oxiracetam were about 8.0%and 7.4%calculated by the normal or degraded oxiracetam injections,whichwere far less than the value of 75%reported in literature,indicating the necessity of further study.
文摘OBJETTIVE: To observe the effects of Yinxingdamo Injection combined with oxiracetam capsule on cognitive function and neurological deficit in patients with acute cerebral infarction. METHODS: A total of 76 patients with acute cerebral infarction were randomly divided into observation group and control group, with 38 patients in each group. Patients in the control group were treated with conventional western medicine and oxiracetam capsules while patients in the observation group were given Yinxingdamo injection intravenous drip treatment on the basis of the same treatment. After 4 weeks of treatment, the cognitive function of the two groups before and after treatment was observed [Simple Intelligence Scale(MMSE Score), Montreal Cognitive Assessment Scale(MoCA Score)], Neurological Deficit [Chinese Stroke Scale(CSS Score), Daily Life Activity ability(ADL score)], free radical biochemical indicators [malondialdehyde(MDA), oxide dismutase(SOD)] changes, and statistical effects of two groups. RESULTS: After treatment, the total effective rate of the observation group was 92.1%, which was significantly higher than 73.7% of the control group(P < 0.05). The MMSE score and MoCA score of the two groups were significantly increased after treatment(P < 0.05), and the MMSE score and MoCA score inobservation group were significantly increased after treatment than the control group(P < 0.05). The CSS scores of the two groups were significantly decreased after treatment(P < 0.05), and the ADL scores were significantly increased(P < 0.05). The improvement of CSS score and ADL score in the observation group were significantly better than those in the control group(P < 0.05), and serum MDA levels were significantly decreased in both groups after treatment(P < 0.05), and SOD levels were significantly increased(P < 0.05), and the improvement of MDA and SOD levels in the observation group was significantly better than that in the control group group(P < 0.05). CONCLUSION: Yinxingdamo injection combined with oxiracetam capsule can effectively inhibit the oxygen free radical reaction injury in patients with acute cerebral infarction, and significantly improve the symptoms of cognitive dysfunction and neurological deficit in patients. Its curative effect is exact and worthy of clinical application.
