Aim To study the pharmacokinetics of oxiracetam after single and multipleintravenous administrations in healthy volunteers. Method A HPLC method was used to determine theserum concentration of oxiracetam after intrave...Aim To study the pharmacokinetics of oxiracetam after single and multipleintravenous administrations in healthy volunteers. Method A HPLC method was used to determine theserum concentration of oxiracetam after intravenous single dose and daily dose of 2 000 mg for 7 din ten Chinese healthy volunteers. Pharmacokinetic analysis was carried out using Drug And Statisticsoftware. Results The AUC_(0-12), AUC_(0-∞), K_e, t_(1/2), MRT after a single dose of 2 000 mgoxiracetam were 256.26 ± 16.84 μg·mL^(-1)·h, 276.74 ±18.11 μg·mL^(-1)·h, 0.18 ±0.03 h^(-1),3.84±0.64 h, and 4.39 10.39 h, and after multiple doses of oxiracetam were 259.36 ±25.43μg·mL^(-1)·h, 285.59 ±27.38 μg·mL^(-1)·h, 0.17 ±0.04 h^(-1), 4.14 ± 0.82 h, and 4.87 ±0.69 h, respectively. Conclusion The pharmacokinetic parameters of oxiracetam do not differremarkably after single and multiple intravenous administration and there is accumulation in serumafter 2 000 mg multiple intravenous administration once a day fof 7 d.展开更多
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
To assess the efficacy and safety of L-oxiracetam,a novel nootropic agent,in improving cognition in patients with TBI,we performed a multicentre,double-blind,randomized controlled trial in China.Participants aged 18 t...To assess the efficacy and safety of L-oxiracetam,a novel nootropic agent,in improving cognition in patients with TBI,we performed a multicentre,double-blind,randomized controlled trial in China.Participants aged 18 to 75 years with TBI(Glasgow Coma Scale score of 10 to 15)were recruited from 51 hospitals from 2019 to 2024.Patients were randomly assigned to Loxiracetam,4 g/day,oxiracetam 6 g/day,or placebo in 2:2:1.The primary outcome was the change in the Loewenstein Occupational Therapy Cognitive Assessment(LOTCA)score from baseline to 90 days post treatment.Secondary outcomes included changes in additional cognitive evaluations,neurological function,activities of daily living(ADL),and adverse events(AEs).The trial was approved by the China National Medical Products Administration(2016L03521),and registered at Clinicaltrials.gov(NCT04205565)and Chinadrugtrials.org.cn(CTR20192539).Five hundred and ninety patients were included(mean age(SD),50.9(14.5);421 males).The least squares(LS)mean of LOTCA change from baseline to 90 days post treatment was 20.45(95%confidence interval[CI]17.23,23.66)in the L-oxiracetam group,15.90(95%CI 12.71,19.10)in the oxiracetam group,and 11.47(95%CI 7.75,15.20)in the placebo group(P value<0.05 for all groups).The LS mean difference of the L-oxiracetam was significantly higher than the placebo group(8.97,95%CI 5.69,12.26;P<0.001;Cohen’s d=0.48[95%CI:0.26,0.69])and the oxiracetam group(4.54,95%CI 1.85,7.23).Secondary efficacy outcomes did not differ between the L-oxiracetam and oxiracetam groups.The proportion of serious AEs did not differ among the three groups.L-oxiracetam could improve cognitive function in patients with mild-to-moderate TBI.L-oxiracetam might be more efficacious than oxiracetam.No significant safety concerns were reported.Despite limitations such as loss to followup,the findings of this study provide important evidence for the clinical management of cognitive dysfunction following TBI.Future studies in real-world clinical settings are warranted to further substantiate the efficacy of L-oxiracetam and oxiracetam.展开更多
目的探讨奥拉西坦联合银杏叶提取物治疗非痴呆型血管性认知障碍(vascular cognitive im pairment non-dementia,VCIND)的疗效及对神经电生理指标的影响。方法采用前瞻性研究方法,按照随机数字表法将于秦皇岛市第一医院2023年1月至2024...目的探讨奥拉西坦联合银杏叶提取物治疗非痴呆型血管性认知障碍(vascular cognitive im pairment non-dementia,VCIND)的疗效及对神经电生理指标的影响。方法采用前瞻性研究方法,按照随机数字表法将于秦皇岛市第一医院2023年1月至2024年12月就诊的152例VCIND患者分为奥拉西坦组(76例)和联合组(76例)。奥拉西坦组接受奥拉西坦治疗,联合组接受奥拉西坦联合银杏叶提取物治疗,观察并比较奥拉西坦组和联合组的认知量表评分、神经电生理指标、血流动力学指标、血清学指标及安全性。结果治疗后,联合组蒙特利尔认知评估量表、简易精神状态检查表、改良Barthel指数评分[分别为(24.52±1.73)、(23.48±1.69)、(79.04±4.74)分]均高于奥拉西坦组[分别为(21.06±1.62)、(20.06±1.63)、(74.58±4.33)分](t=12.727、12.698、6.056,均P<0.05)。治疗后,联合组诱发电位P300潜伏期和θ/α功率比值[分别为(291.54±18.62)ms、(1.27±0.36)]均低于奥拉西坦组[分别为(328.63±19.54)ms、(1.54±0.43)](t=11.980、4.197,均P<0.05),电位波幅和α波相对功率[分别为(8.11±1.85)μV、(35.26±5.18)%]均高于奥拉西坦组[分别为(6.36±1.48)μV、(30.17±4.82)%](t=6.439、6.271,均P<0.05)。治疗后,联合组平均血流速度为(66.74±6.48)cm/s高于奥拉西坦组(62.83±6.52)cm/s(t=3.708,P<0.05),搏动指数和阻力指数[分别为(1.03±0.12)、(0.64±0.14)]均低于奥拉西坦组[分别为(1.17±0.18)、(0.73±0.16)](t=5.642、3.690,均P<0.05)。治疗后,联合组白细胞介素6、神经元特异性烯醇化酶及同型半胱氨酸[分别为(7.74±5.48)μg/L、(14.03±3.12)ng/mL、(11.64±3.14)μmol/L]均低于奥拉西坦组[分别为(10.83±5.52)μg/L、(16.17±3.18)ng/mL、(15.73±3.16)μmol/L](t=3.463、4.188、8.004,均P<0.05)。奥拉西坦组和联合组不良反应发生率差异无统计学意义[5.26%(4/76)vs 7.89%(6/76)](χ^(2)=0.428,P>0.05)。结论奥拉西坦联合银杏叶提取物治疗VCIND的疗效较好,能有效改善患者认知功能、日常生活能力、脑血流动力学及神经电生理指标,并具有神经保护及抑制炎症等多重机制,且安全性良好。展开更多
文摘Aim To study the pharmacokinetics of oxiracetam after single and multipleintravenous administrations in healthy volunteers. Method A HPLC method was used to determine theserum concentration of oxiracetam after intravenous single dose and daily dose of 2 000 mg for 7 din ten Chinese healthy volunteers. Pharmacokinetic analysis was carried out using Drug And Statisticsoftware. Results The AUC_(0-12), AUC_(0-∞), K_e, t_(1/2), MRT after a single dose of 2 000 mgoxiracetam were 256.26 ± 16.84 μg·mL^(-1)·h, 276.74 ±18.11 μg·mL^(-1)·h, 0.18 ±0.03 h^(-1),3.84±0.64 h, and 4.39 10.39 h, and after multiple doses of oxiracetam were 259.36 ±25.43μg·mL^(-1)·h, 285.59 ±27.38 μg·mL^(-1)·h, 0.17 ±0.04 h^(-1), 4.14 ± 0.82 h, and 4.87 ±0.69 h, respectively. Conclusion The pharmacokinetic parameters of oxiracetam do not differremarkably after single and multiple intravenous administration and there is accumulation in serumafter 2 000 mg multiple intravenous administration once a day fof 7 d.
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.
文摘To assess the efficacy and safety of L-oxiracetam,a novel nootropic agent,in improving cognition in patients with TBI,we performed a multicentre,double-blind,randomized controlled trial in China.Participants aged 18 to 75 years with TBI(Glasgow Coma Scale score of 10 to 15)were recruited from 51 hospitals from 2019 to 2024.Patients were randomly assigned to Loxiracetam,4 g/day,oxiracetam 6 g/day,or placebo in 2:2:1.The primary outcome was the change in the Loewenstein Occupational Therapy Cognitive Assessment(LOTCA)score from baseline to 90 days post treatment.Secondary outcomes included changes in additional cognitive evaluations,neurological function,activities of daily living(ADL),and adverse events(AEs).The trial was approved by the China National Medical Products Administration(2016L03521),and registered at Clinicaltrials.gov(NCT04205565)and Chinadrugtrials.org.cn(CTR20192539).Five hundred and ninety patients were included(mean age(SD),50.9(14.5);421 males).The least squares(LS)mean of LOTCA change from baseline to 90 days post treatment was 20.45(95%confidence interval[CI]17.23,23.66)in the L-oxiracetam group,15.90(95%CI 12.71,19.10)in the oxiracetam group,and 11.47(95%CI 7.75,15.20)in the placebo group(P value<0.05 for all groups).The LS mean difference of the L-oxiracetam was significantly higher than the placebo group(8.97,95%CI 5.69,12.26;P<0.001;Cohen’s d=0.48[95%CI:0.26,0.69])and the oxiracetam group(4.54,95%CI 1.85,7.23).Secondary efficacy outcomes did not differ between the L-oxiracetam and oxiracetam groups.The proportion of serious AEs did not differ among the three groups.L-oxiracetam could improve cognitive function in patients with mild-to-moderate TBI.L-oxiracetam might be more efficacious than oxiracetam.No significant safety concerns were reported.Despite limitations such as loss to followup,the findings of this study provide important evidence for the clinical management of cognitive dysfunction following TBI.Future studies in real-world clinical settings are warranted to further substantiate the efficacy of L-oxiracetam and oxiracetam.
