Objective To evaluate the efficacy and safety of Shengmai injection for hypoxic-ischemic encephalopathy (HIE). Methods We searched MEDLINE (1966 to February 2007), EMBASE (1980 to February 2007), CBM (1978 to 2006), CNKI (1979 to February 2007), VIP (1989 to February 2007), and handsearched five Journals on Pediatrics. We evaluated features of quality of included studies, including randomization, blinding, allocation concealment and loss of follow-up. Meta-analyses were performed using The Cochrane Collaboration’s RevMan 4.2.8. Results Seven randomized controlled trials were included. The cure rate on day 5 in the Shengmai injection group was higher than in the control group (RR 1.55, 95%CI 1.25 to 1.93), but this rate was similar on day 10 (RR 0.74, 95%CI 0.43 to 1.29). No significant difference in cure rate was noted between the Shengmai injection group and naloxone group (RR 0.88, 95%CI 0.53 to 1.46). No significant differences were observed in mortality (RR0.44, 95%CI 0.16 to 1.19) and mutilation rate (RR 0.58, 95%CI 0.21 to 1.56) between the Shengmai injection group and the control group. For those babies suffering from HIE combined with myocardial damage, Shengmai injection could speed up the recovery of ECG (WMD=–2.02, 95%CI –2.76 to –1.28) and myocardial enzymogram (CK-MB: WMD= –4.78, 95%CI –6.77 to –2.79; CK-BB: WMD=–2.68, 95%CI –4.58 to –0.78). Significant differences in NBNA score were noted between the Shengmai injection group and the control group on day 5 (WMD=4.05, 95%CI 2.47 to 5.63) and day 10 (WMD=3.50, 95%CI 2.26 to 4.74). No fatal side effects were reported. Conclusions Shengmai injection has certain therapeutic values in treating HIE. Shengmai injection can speed up the recovery ECG, CK-BM and CK-BB of HIE patients, especially in those who have myocardial damage. Shengmai injection can also improve the NBNA score. However, because of the low statistical power and high risks for selection bias, performance bias and measurement bias in the included trials, these conclusions need to be interpreted cautiously.
药物上市前须经过人体试验，参与药物临床试验的受试者将承担不同程度的风险，我国GCP明确规定要充分保障受试者的权益，伦理委员会和知情同意书是保障受试者权益的主要措施，但在实际中仍存在不少问题。为此，如何切实保障受试者的权益，是临床试验所要解决的一个重要问题。
Objective To assess the tolerability and safety of Yinhuang injection in Chinese healthy volunteers. Methods Thirty-two healthy subjects were enrolled in the single-dose study. Each subject was administered one of the seven doses of 40, 120, 240, 320, 400, 480, and 560 mg, respectively, by intravenous injection. The sample sizes were 2, 4, 6, 6, 6, 4 and 4, respectively, for each dose group. Twelve healthy subjects were enrolled in the multi-dose study. The subjects in the lower dose group were administered 240 mg and the subjects in the higher dose group were administered 400 mg Yinhuang by intravenous injection once a day for consecutive 7 days. The sample sizes for both groups were 6. The safety was evaluated based on clinical symptoms, vital signs, physical examinations, electrocardiogram (ECG), laboratory tests and adverse events. All analyses were performed by using the software package SAS version 9.1. T-test and analysis of variance were used for continuous variables. Chi-square test and Fisher’s exact test were used for categorical variables.Results A total of 44 healthy volunteers completed the tolerance test. No serious adverse event and clinically significant changes in vital signs, ECG and laboratory tests were found in both single-dose groups and multi-dose groups. Among two mild adverse events, dizziness occurred in one subject in 480 mg dose group in the single-dose trial, which was probably related to the experimental drug. Conclusion Yinhuang injection is safe and well-tolerated in Chinese healthy subjects after administration of single-doses (40-560 mg) and multi-doses (240-400 mg once a day for consecutive 7 days). The maximum-tolerated dose of Yinhuang injection is at 560 mg in the single-dose trial. The dose regimen of 240-400 mg a day is recommended for phase II study.
目的 采用高效液相色谱-质谱联用法研究盐酸多奈哌齐口腔崩解片的人体药物代谢动力学，并评价其生物等效性。 方法 2009年9月－11月对22例健康男性受试志愿者单次交叉口服盐酸多奈哌齐口腔崩解片（试验制剂）和盐酸多奈哌齐普通片（参比制剂），测定给药后不同时间点血浆中多奈哌齐经时血药浓度，采用DAS 2.0软件进行药物代谢动力学参数计算和生物等效性评价。 结果 受试者单次口服试验制剂与参比制剂后，达峰时间分别为（2.95 ± 1.16）、（3.19 ± 0.98） h，峰浓度分别为（9.98 ± 2.93）、（9.13 ± 2.05） ng/mL，药时曲线下面积（0-t）分别为（470.76± 142.64）、（446.57 ± 137.30）ng/mL·h；药时曲线下面积（0-∞）分别为（517.74 ± 169.79）、（489.47 ± 162.13）ng/mL·h。试验制剂与参比制剂的生物等效性结果为104.7%，其90%置信区间为（98.4%，111.4%）。结论 盐酸多奈哌齐口腔崩解片与普通片生物等效。
目的 采用高效液相色谱法测定受试者口服埃索美拉唑肠溶胶囊与埃索美拉唑镁肠溶片后血药浓度，评价埃索美拉唑肠溶胶囊的生物等效性。 方法 2009年9月－10月，36例健康男性受试者单次交叉口服埃索美拉唑肠溶胶囊（试验制剂）和埃索美拉唑镁肠溶片（参比制剂），测定给药后不同时间点血浆中埃索美拉唑经时血药浓度，采用DAS 2.0软件进行药物代谢动力学参数计算和生物等效性评价。 结果 受试者单次口服试验制剂与参比制剂后，达峰时间分别为（2.19 ± 0.96）、（2.43 ± 0.92） h，峰浓度分别为（1 748.86 ± 615.81）、（1 442.92 ± 476.41） μg/L，药时曲线下面积（AUC）0-t分别为（3 927.14 ± 1 839.10）、（3 878.79 ± 1 734.84） μg/L·h，AUC0-∞分别为（3 998.36 ± 1 866.22）、（3 918.31 ± 1 773.44） μg/L·h。试验制剂与参比制剂的生物等效性为94.0%，其90%CI为（82.3%，107.2%）。 结论 埃索美拉唑肠溶胶囊与埃索美拉唑镁肠溶片生物等效。
目的 采用高效液相色谱-质谱联用法（HPLC-MS/MS）研究普罗布考片的人体药物代谢动力学变化规律。 方法 2010年10月－11月，24例健康男性受试者单次口服普罗布考片0.5 g，采用HPLC-MS/MS法测定给药后不同时间点血浆中普罗布考的经时血药浓度，采用DAS 2.0软件进行药动学参数计算。 结果 受试者单次口服普罗布考片，达峰时间为（11.50 ± 6.66）h，峰浓度为（2 894.72 ± 1 320.53）ng/mL，药-时曲线下面积（AUC）0-t为（238 876.96 ± 131 873.67） ng/mL· h，AUC0-∞为（259 989.08 ± 146 112.88）ng/mL· h，半衰期为（278.52 ± 164.72） h。结论 普罗布考片体内过程符合二室模型，单次口服具有较好的安全性。
【摘要】 目的 评价麻敏维C缓释胶囊（每粒含盐酸伪麻黄碱90 mg和马来酸氯苯那敏4 mg）在人体的生物等效性。 方法 于2006年6月采用随机交叉自身前后对照试验设计，26例受试者分别单次和多次空腹口服麻敏维C缓释胶囊（试验制剂）和复方盐酸伪麻黄碱缓释胶囊（参比制剂），与不同时间点取血样，采用液-质联用（HPLC/MS）法测定人血浆中盐酸伪麻黄碱和马来酸氯苯那敏的浓度，以DAS软件计算药物代谢动力学参数，并进行生物等效性评价。 结果 单次给药后，两组分的主要药物代谢动力学参数无统计学意义（Pgt;0.05）。试验制剂中马来酸氯苯那敏和盐酸伪麻黄碱生物利用度分别为104.31%和109.19%。多次给药后，两组分的主要药物代谢动力学参数无统计学意义（Pgt;0.05）。试验制剂的马来酸氯苯那敏和盐酸伪麻黄碱的生物利用度分别为103.58%和99.37%。 结论 麻敏维C缓释胶囊和复方盐酸伪麻黄碱缓释胶囊具有生物等效性。【Abstract】 Objective To investigate the bioequivalence of delayed-release capsule of ephedrine-chlorphenamine-vitamin C. Methods In June 2006, 26 healthy volunteers were administrated with delayed-release capsule of ephedrine-chlorphenamine-vitamin C or delayed-release capsule of ephedrine-chlorphenamine in a randomized and two-way crossover design with single or multiple dosage. The plasma concentrations were determined by HPLC/MS method. The pharmacokinetic parameters and bioequivalence were calculated by DAS software. Results After single dose administration, no significant differences were found in tmax, Cmax, t1/2, and AUC0-t between the two preparations. The relative bioavailability of the test preparation was 104.31% in chlorphenamine and 109.19% in ephedrine, respectively. After multiple dose administration, no significant differences were found in tmax, Cmax, t1/2, and AUC0-t between the two preparations. The relative bioavailability of the test preparation was 103.58% in chlorphenamine and 99.37% in ephedrine, respectively. Conclusion Delayed-release capsule of ephedrine-chlophenamine-vitamin C is equivalent to the reference preparation.