Objective:To evaluate the bioequivalence and safety of domestic and original pyrazinamide tablets under fasting condition.Methods:A single center, randomized, open-label, two period self-crossover trial was conducted in healthy adult volunteers. The test preparation (T) of pyrazinamide tablets was produced by Taicang Pharmaceutical Factory and the reference preparation (R) was produced by A&Z Pharmaceutical Inc. (Pyrazinamide ?). The healthy subjects were randomly divided into 2 groups and took the drugs for 2 times with different order in each group, which were R-T group (subjects took R on day 1 and then T on day 8) and T-R group (subjects took T on day 1 and then R on day 8). Pharmacokinetic parameters were used as endpoints to assess the bioequivalence. Peripheral venous blood samples (3 ml) were collected from subjects within 1 hour before taking the drug and at 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, and 210 minutes and 4, 5, 6, 8, 12, 24, 36, and 48 hours after taking the drug. Plasma was frozen after centrifugation of the blood samples. The plasma pyrazinamide concentrations were determined by a tandem liquid chromatography-mass spectrometry method and the main pharmacokinetic parameters such as peak concentration ( Cmax) and the area under the concentration-time curve (AUC), including AUC from time zero (pre-dose) to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞), were calculated. The test and reference preparations were judged as bioequivalence when the 90% confidence intervals ( CI) of geometric mean ratios for AUC 0-t, AUC 0-∞, and Cmax all ranged from 0.80 to 1.25. Adverse events occurred in subjects during the trial were observed and recorded. Results:A total of 24 healthy volunteers were enrolled in the trial, including 16 males and 8 females aged 18-50 years, with 12 in the R-T and T-R groups, respectively. All subjects completed the trial. After taking medicine under fasting condition, the 90% CI of the geometric mean ratios of Cmax, AUC 0-t, and AUC 0-∞ for the test and reference preparations were 0.93-1.09, 0.98-1.03, and 0.98-1.03, respectively. During the trial, the incidence of adverse events was 25.0% (6/24) and 3 cases occurred after taking the test and reference preparations respectively, which were grade 1 in severity. Conclusion:The domestic and original pyrazinamide tablets were bioequivalence and with good safety when taken under fasting condition.

Objective:To evaluate the bioequivalence and safety of domestic and original pyrazinamide tablets under fasting condition.Methods:A single center, randomized, open-label, two period self-crossover trial was conducted in healthy adult volunteers. The test preparation (T) of pyrazinamide tablets was produced by Taicang Pharmaceutical Factory and the reference preparation (R) was produced by A&Z Pharmaceutical Inc. (Pyrazinamide ?). The healthy subjects were randomly divided into 2 groups and took the drugs for 2 times with different order in each group, which were R-T group (subjects took R on day 1 and then T on day 8) and T-R group (subjects took T on day 1 and then R on day 8). Pharmacokinetic parameters were used as endpoints to assess the bioequivalence. Peripheral venous blood samples (3 ml) were collected from subjects within 1 hour before taking the drug and at 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, and 210 minutes and 4, 5, 6, 8, 12, 24, 36, and 48 hours after taking the drug. Plasma was frozen after centrifugation of the blood samples. The plasma pyrazinamide concentrations were determined by a tandem liquid chromatography-mass spectrometry method and the main pharmacokinetic parameters such as peak concentration ( Cmax) and the area under the concentration-time curve (AUC), including AUC from time zero (pre-dose) to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞), were calculated. The test and reference preparations were judged as bioequivalence when the 90% confidence intervals ( CI) of geometric mean ratios for AUC 0-t, AUC 0-∞, and Cmax all ranged from 0.80 to 1.25. Adverse events occurred in subjects during the trial were observed and recorded. Results:A total of 24 healthy volunteers were enrolled in the trial, including 16 males and 8 females aged 18-50 years, with 12 in the R-T and T-R groups, respectively. All subjects completed the trial. After taking medicine under fasting condition, the 90% CI of the geometric mean ratios of Cmax, AUC 0-t, and AUC 0-∞ for the test and reference preparations were 0.93-1.09, 0.98-1.03, and 0.98-1.03, respectively. During the trial, the incidence of adverse events was 25.0% (6/24) and 3 cases occurred after taking the test and reference preparations respectively, which were grade 1 in severity. Conclusion:The domestic and original pyrazinamide tablets were bioequivalence and with good safety when taken under fasting condition.

Objective:To evaluate the postprandial bioequivalence of domestic and original glucosamine sulfate capsules in Chinese healthy volunteers.Methods:The trial was a single-center, randomized, open-label, single-dose, 2-preparation, 3-sequence, 3-period, partially repeated crossover design. The trialed drugs were domestic glucosamine sulfate capsules Yisuojia (test preparation) and original glucosamine sulfate capsules Viartril ? (reference preparation). Healthy subjects were randomly divided into 3 groups, each group took medicine in 3 periods, but the order of taking test preparation (T) and reference preparation (R) was different, which were TRR, RTR and RRT groups. The healthy volunteers in the TRR, RTR, and RRT groups received the trialed drugs orally 30 minutes after diet supply on day 1, 4, and 7, respectively. Peripheral venous blood samples 4 ml were collected at 1-2 hours after dinner the day before medication (baseline 1), within 60 minutes before medication (baseline 2), and 15, 30, 45, 60, 90, 120, and 150 minutes and 3, 4, 5, 6, 8, 10, 14, and 16 hours after medication, respectively. Plasma was collected after centrifugation, frozen, and stored. Liquid chromatography-tandem mass spectrometry was used for the determination of glucosamine concentrations in plasma samples and main pharmacokinetic parameters such as the area under the concentration-time curve(AUC), including areas from time zero (pre-dose) to the last measurable concentration (AUC 0-t) and extrapolated to infinite time (AUC 0-∞), and peak concentration ( Cmax) were calculated. Because glucosamine was an endogenous substance in humans, the measured blood concentration of glucosamine was corrected by subtracting the baseline value before medication (the average of baseline 1 and baseline 2). The test and reference preparations were equivalent when the geometric mean ratios ( GMR) and their 90% confidence intervals ( CI) for AUC 0-t, AUC 0-∞, and Cmax all ranged from 0.800 to 1.250. Results:A total of 30 healthy volunteers were enrolled in the study, including 20 males and 10 females, aged (31±7) years with a range of 18-45 years. Ten volunteers were included in each TRR, RTR, and RRT group. One volunteer fell off in the TRR group after the first period of medication and the remaining 29 volunteers completed the trial. The baseline uncorrected GMR (90 %CI) of AUC 0-t, AUC 0-∞, and Cmax for the test and the reference preparations were 0.985 (0.941-1.031), 1.014 (0.961-1.070), and 0.937 (0.827-1.062), respectively; the baseline corrected GMR (90 %CI) of AUC 0-t, AUC 0-∞, and Cmax of the test and the reference preparations were 0.977 (0.923-1.035), 0.976 (0.922-1.032), and 0.932 (0.817-1.063), respectively, which all fell within the equivalence range (0.800-1.250). During the trial, no adverse events related to the trialed drugs occurred in the 3 groups. Conclusion:Domestic glucosamine sulfate capsules were bioequivalent to the original when taken after diet and had a good safety profile.

Objective:To evaluate the postprandial bioequivalence of domestic and original glucosamine sulfate capsules in Chinese healthy volunteers.Methods:The trial was a single-center, randomized, open-label, single-dose, 2-preparation, 3-sequence, 3-period, partially repeated crossover design. The trialed drugs were domestic glucosamine sulfate capsules Yisuojia (test preparation) and original glucosamine sulfate capsules Viartril ? (reference preparation). Healthy subjects were randomly divided into 3 groups, each group took medicine in 3 periods, but the order of taking test preparation (T) and reference preparation (R) was different, which were TRR, RTR and RRT groups. The healthy volunteers in the TRR, RTR, and RRT groups received the trialed drugs orally 30 minutes after diet supply on day 1, 4, and 7, respectively. Peripheral venous blood samples 4 ml were collected at 1-2 hours after dinner the day before medication (baseline 1), within 60 minutes before medication (baseline 2), and 15, 30, 45, 60, 90, 120, and 150 minutes and 3, 4, 5, 6, 8, 10, 14, and 16 hours after medication, respectively. Plasma was collected after centrifugation, frozen, and stored. Liquid chromatography-tandem mass spectrometry was used for the determination of glucosamine concentrations in plasma samples and main pharmacokinetic parameters such as the area under the concentration-time curve(AUC), including areas from time zero (pre-dose) to the last measurable concentration (AUC 0-t) and extrapolated to infinite time (AUC 0-∞), and peak concentration ( Cmax) were calculated. Because glucosamine was an endogenous substance in humans, the measured blood concentration of glucosamine was corrected by subtracting the baseline value before medication (the average of baseline 1 and baseline 2). The test and reference preparations were equivalent when the geometric mean ratios ( GMR) and their 90% confidence intervals ( CI) for AUC 0-t, AUC 0-∞, and Cmax all ranged from 0.800 to 1.250. Results:A total of 30 healthy volunteers were enrolled in the study, including 20 males and 10 females, aged (31±7) years with a range of 18-45 years. Ten volunteers were included in each TRR, RTR, and RRT group. One volunteer fell off in the TRR group after the first period of medication and the remaining 29 volunteers completed the trial. The baseline uncorrected GMR (90 %CI) of AUC 0-t, AUC 0-∞, and Cmax for the test and the reference preparations were 0.985 (0.941-1.031), 1.014 (0.961-1.070), and 0.937 (0.827-1.062), respectively; the baseline corrected GMR (90 %CI) of AUC 0-t, AUC 0-∞, and Cmax of the test and the reference preparations were 0.977 (0.923-1.035), 0.976 (0.922-1.032), and 0.932 (0.817-1.063), respectively, which all fell within the equivalence range (0.800-1.250). During the trial, no adverse events related to the trialed drugs occurred in the 3 groups. Conclusion:Domestic glucosamine sulfate capsules were bioequivalent to the original when taken after diet and had a good safety profile.

Objective:To explore the principles and elements of ethical review of clinical trials regarding medical apparatus and instruments.Methods:This paper introduced Beijing Anzhen Hospital's requirements on considerations for the vulnerable,acquisition of informed consent,the researchers' qualification and experiment design,during ethical review of clinical trials regarding medical apparatus and instruments.Results:Institution review board of Beijing Anzhen Hospital designed principles and standard operating procedures for ethical review of clinical trials regarding medical apparatus and instruments.Conclusion:Ethical review of clinical trials regarding medical apparatus and instruments now is more scientifically standardized,and has become an important approach for the protection of subjects' rights and interests.

Objective To study the effects of treadmill training on the recovery of neurological function and the expression of IGF-1/IGF-1Rin the brain poat focal cerebral ischemia.Metheods Forty-two male,adult Sprague-Dawley rats were randomly divided into a sham group(n=6),a model group(n=18)and a treadmill exercises group(n=18).Focal cerebral ischemia was induced in the latter two groups by right middle cerebral artery occlusion(MCAO)using a modified Longa's metheod.The rats in the treadmill exercises group were given treadmill training 6 days a week for 4weeks beginning 24 h after the MCAO. Rats in the sham group and model groups were reared in standard cages and could move frddly. Before being sacrificed at the 7th 14th and 28th day after the MCAO,the rats' neurological function were tested giving modified neurological weverity scores (mNSS). The expression of IGF-1/IGF-1R was detected using the reverse transcriptsae polymersae chain reaction and immunohistochemical methods.Results Neurological runction in the exercises group at the 14th and 28th day was better than in the control group,and IGF-1 and IGF-1Rexpression were significcantly upregulated on the 7th,14th and 28th day after the MCAO.Conclusion Treadmill training can improve neurological function by upregulating the expression of IGF-1 and IGF-1R in the ischemic brain, at least in rats.