正清风痛宁肠溶片在Beagle犬体内的药动学和生物等效性研究

目的:研究正清风痛宁肠溶片在Beagle犬体内的药动学和生物等效性。方法:选用10只Beagle犬,单剂量随机交叉灌胃正清风痛宁肠溶片受试制剂或参比制剂(10mg·kg-1),用高效液相色谱法测定血药浓度,3p97软件计算药动学参数和生物利用度。结果:受试制剂与参比制剂的药-时曲线呈一室模型,主要药动学参数tmax分别为(86.25±10.61)min和(75.00±16.04)min,Cmax分别为(0.18±0.038)μg·mL-1和(0.18±0.042)μg·mL-1,t1/2Ke分别为(78.34±15.21)min和(88.77±30.90)min,AUC0～T分别为(30.31±7.82)μg·min·mL-1和(32.09±8.61)μg·min·mL-1;受试制剂相对生物利用度为(94.45±5.49)%。结论:受试制剂与参比制剂具有生物等效性。     

青藤碱肠溶片在Beagle犬体内药动学研究

目的:研究口服青藤碱肠溶片在Beagle犬体内的药动学。方法:8只Beagle犬口服青藤碱肠溶片(10mg·kg-1)0、15、30、60、90、120、240、480min后分别从前肢静脉取血2mL,采用高效液相色谱法测定并计算血药浓度,用3p97软件计算药动学参数。结果:青藤碱肠溶片在犬体内药-时曲线符合一室模型,主要药动学参数tmax为(69.66±16.41)min,Cmax为(0.13±0.02)μg·mL-1,t1/2ke为(87.62±28.26)min,AUC0～T为(28.43±3.48)μg·min·mL-1。结论:Beagle犬口服青藤碱肠溶片后在体内吸收迅速,消除较快。     

2种丙泊酚注射液犬体内药动学研究

目的:比较2种丙泊酚制剂在犬体内的药动学情况。方法:12只Beagle犬随机交叉单次静脉注射丙泊酚微乳注射液或丙泊酚脂肪乳注射液4mg·kg-1后,采用高效液相色谱法测定丙泊酚血药浓度,用3p97软件计算主要药动学参数,并进行比较。结果:丙泊酚微乳注射液和丙泊酚脂肪乳注射液的药-时曲线均呈二室模型,二者t1/2β分别为(46.40±41.77)、(62.75±51.85)min;AUC(0～)t分别为(27.67±9.60)、(21.90±10.10)μg·min·mL-1,AUC(0～∞)分别为(29.33±13.55)、(28.66±13.76)μg·min·mL-1;经方差分析、双单侧t检验及(1-2α)置信区间法统计分析,药动学参数AUC(0～∞)间无显著性差异(P>0.05)。结论:2种丙泊酚制剂在犬体内的药动学过程相近。     

盐酸伐昔洛韦片人体生物等效性研究

目的研究盐酸伐昔洛韦片在健康人体内的生物等效性。方法20名受试者单剂量、交叉口服盐酸伐昔洛韦片受试制剂和参比制剂后,采用高效液相色谱-荧光检测法测定其体内代谢转化物阿昔洛韦的血药浓度,以BAPP2.0程序计算药动学参数和生物等效性数据。结果受试制剂和参比制剂的阿昔洛韦,其Cmax分别为(2.04±0.48)、(1.94±0.37)μg·mL-1,tmax分别为(1.3±0.6)、(1.4±0.6)h,t1/2分别为(2.53±0.42)、(2.55±0.43)h,AUC0～12分别为(5.82±0.99)、(5.54±0.84)μg·h·mL-1,AUC0～∞分别为(6.04±1.04)、(5.76±0.94)μg·h·mL-1。经方差分析和配对t检验,受试制剂与参比制剂的药动学参数无显著性差异(P>0.05),受试制剂的相对生物利用度为(105.7±13.9)%。结论2种制剂具有生物等效性。     

匹多莫德干混悬剂人体药动学及生物等效性研究

目的:研究匹多莫德干混悬剂在健康人体的药动学及生物等效性。方法:健康男性志愿者20名,随机交叉单剂量口服匹多莫德干混悬剂(受试制剂)和颗粒剂(参比制剂)各0.8g,采用液-质联用法测定血浆中匹多莫德的浓度。应用DAS软件计算药动学参数和相对生物利用度,评价其生物等效性。结果:口服受试制剂和参比制剂后的主要药动学参数:t1/2分别为(1.84±0.35)、(1.93±0.51)h;tmax分别为(2.23±0.82)、(2.25±1.01)h;Cmax分别为(4.72±1.75)、(4.72±2.16)μg·mL-1;AUC0～20分别为(22.34±6.97)、(21.07±8.04)μg·h·mL-1;AUC0～∞分别为(23.01±7.10)、(21.74±8.14)μg·h·mL-1。受试制剂相对于参比制剂的生物利用度为(111.2±31.7)%。结论:2种制剂具有生物等效性。     

酮洛芬脉冲控释片在家犬体内的药动学及生物利用度研究

目的:考察酮洛芬脉冲控释片在家犬体内的药动学及生物利用度。方法:将6只犬随机均分为2组,分别口服受试制剂酮洛芬脉冲控释片和参比制剂酮洛芬肠溶胶囊150mg,1周后2组交叉试验。给药后不同时间点取样,采用高效液相色谱法测定血样中酮洛芬浓度并计算药动学参数及比较体内、外相关性。结果:受试制剂与参比制剂的tmax分别为(5.00±0.41)、(3.75±0.00)h;Cmax分别为(15.40±1.94)、(20.73±1.72)μg·mL-1,AUC0～t分别为(101.33±17.49)、(93.21±25.03)μg.h.mL-1,受试制剂相对生物利用度为108.71%,体外释药与体内吸收数据r=0.987,具有较好的相关性。结论:酮洛芬脉冲控释片与酮洛芬肠溶胶囊具有生物等效性。     

盐酸伐昔洛韦片的人体药动学及生物等效性研究

目的:研究单剂量口服盐酸伐昔洛韦片的药动学特征,并评价2种制剂的生物等效性。方法:采用双周期交叉试验方法,18名健康志愿者分别单剂量口服2种盐酸伐昔洛韦片600mg,采用高效液相色谱法测定血浆中药物浓度,计算药动学参数,并进行统计分析。结果:盐酸伐昔洛韦片受试制剂与参比制剂的主要药动学参数tmax分别为(1.69±0.25)、(1.72±0.26)h,Cmax分别为(3.34±0.58)、(3.40±0.49)μg·mL-1,t1/2分别为(2.73±0.31)、(2.97±0.33)h,AUC0～14分别为(11.22±2.21)、(11.12±1.90)μg·h·mL-1,AUC0～∞分别为(11.76±2.15)、(11.61±1.86)μg·h·mL-1。受试制剂相对于参比制剂的生物利用度为(101.06±11.72)%。结论:2种制剂具有生物等效性。     

盐酸甲氯芬酯胶囊在健康人体内的生物等效性研究

目的:研究2种盐酸甲氯芬酯胶囊在中国健康志愿者体内的生物等效性。方法:18名健康男性志愿者随机分为2组,分别单剂量交叉口服盐酸甲氯芬酯胶囊受试制剂或参比制剂200mg。于服药前0h和服药后0.33、0.67、1、1.5、2、2.5、3、4、6、8、10、14、24h时抽取静脉血,采用高效液相色谱法测定血浆中对氯苯氧乙酸的浓度。通过DASVer2.0软件计算主要药动学参数,评价2制剂的生物等效性。结果:盐酸甲氯芬酯受试制剂与参比制剂的药动学参数分别为:tma(x2.11±0.37)、(2.06±0.34)h,cmax(12.56±2.85)、(12.78±2.84)μg·mL-1,t1/(25.81±2.68)、(6.00±2.14)h,AUC0～2(434.11±7.89)、(34.12±7.99)μg·h·mL-1,AUC0～∞(34.83±7.68)、(34.79±7.97)μg·h·mL-1。以AUC0～24计算,受试制剂对参比制剂的相对生物利用度为(100.7±11.7)%。结论:2种盐酸甲氯芬酯胶囊在中国健康志愿者体内具有生物等效性。     

2种奥美拉唑肠溶胶囊的人体生物等效性研究

目的研究2种奥美拉唑肠溶胶囊的生物等效性。方法20名健康男性志愿者随机分成2组,交叉口服受试制剂和参比制剂各40mg,采用高效液相色谱法测定人血清中奥美拉唑浓度,由DAS软件计算药动学参数及相对生物利用度。结果受试制剂与参比制剂的t1/2分别为(1.685±0.866)、(1.653±0.862)h,tmax分别为(2.425±0.693)、(2.200±0.865)h,Cmax分别为(0.894±0.481)、(0.865±0.342)μg·mL-1,AUC0～10分别为(2.041±1.446)、(2.022±1.322)μg·h·mL-1,AUC0～∞分别为(2.163±1.594)、(2.125±1.507)μg·h·mL-1,受试制剂的相对生物利用度为(100.3±17.4)%。结论2种奥美拉唑肠溶胶囊具有生物等效性。     

雷贝拉唑钠肠溶胶囊Beagle犬体内药动学及生物等效性研究

目的：建立HPLC-MS测定方法分析Beagle犬血浆中雷贝拉唑的含量,并作不同厂家两种雷贝拉唑钠肠溶胶囊的药动学及生物等效性研究。方法：6只Beagle犬随机分为两组,采用单剂量双周期交叉试验,分别口服给予60 mg雷贝拉唑钠肠溶胶囊受试制剂或参比制剂,给药后不同时间点采血,测定血药浓度,利用DAS3.0软件计算药动学参数,并比较两个厂家生产的制剂的生物等效性。结果：Beagle犬单次给予雷贝拉唑钠肠溶胶囊受试制剂和参比制剂后的tmax分别为（3.57±0.91）h和（3.43±0.87）h,Cmax分别为（539.03±129.13）ng·mL-1和（554.90±135.75）ng·mL-1,t1/2分别为（2.20±0.90）h和（2.09±0.78）h,药时曲线下面积AUC（0→24 h）分别为（1341.40±442.03）ng·h·mL-1和（1319.41±402.29）ng·h·mL-1。结论：结果表明不同厂家的两种雷贝拉唑钠肠溶胶囊具有生物等效性。     

Analysis of acamprosate in beagle dog plasma by LC-MS-MS

A rapid, sensitive, and specific analytical method was developed and validated to quantify acamprosate calcium in beagle dog plasma. The method employs a single plasma protein precipitation, and the analytes are separated by chromatography on an Acquity UPLC HSS T3 column and analyzed by mass spectrometry in the multiple reaction monitoring (MRM) mode. The method has a chromatographic run time of 1.25 min and a linear calibration curve over the range 200-10000 ng/mL (r(2)>0.9994). The intra-day and inter-day accuracy and precision were within 10.0% for the analyte. Acamprosate was stable during all sample storage, preparation, and analytical periods. This method was employed in a pharmacokinetic study of an acamprosate 333 mg enteric-coated tablet in 8 male beagle dogs that received single 666 mg doses (333 mg x 2 tablets). The proposed method enables identification and quantification in pharmacokinetic studies of acamprosate in beagle dog plasma.     

尼可地尔口腔速溶片的研究

目的　制备尼可地尔口腔速溶片以提高其生物利用度和改善药物的苦味。方法　用croscarmellosesodium ,D-甘露醇和乳糖制备直径为6mm(崩解时限为12s)和10 mm(崩解时限为23s)的尼可地尔口腔速溶片。对其崩解性能、硬度、药物释放度、体内吸收及口感性能进行了考察。结果　压力在1.37×10⁸ Pa以上,甘露醇-乳糖比为9∶1,croscarmellosesodium的添加量为1% - 4%时,口腔速溶片的崩解时间较市售片缩短了1/3,且能达到一定的硬度。对Beagle犬经口服给药后,测得血药浓度与市售片相同,AUC ,C_max,T_max值无明显差异。口腔速溶片有长效和掩盖药物苦味的作用,同时甜味剂对掩盖药物苦味有相加作用。结论　口腔速溶片为快速崩解型片剂,与市售片等效,适合老龄和小儿患者服用     

银杏叶片治疗急性缺血性脑卒中的疗效观察

摘分为治要疗组目与的对:观照察组银。杏2叶组片患治者疗均急在性发缺病血后性72脑h卒内中给的予临丹床参疗注效射和液安25全0m性L。,静方脉法滴:将注我,q院d;1阿20司例匹急林性肠缺溶血片性0脑.1卒g,中qd患。者治,疗随组机在1此:1基础上加服银杏叶片0.18g,tid。2组疗程均为30d。治疗后,采用神经功能缺损评分判定疗效。结果:治疗组治疗后神经功能缺损评分明显优于对照组,差异有统计学意义(P<0.05)。2组均未见严重不良反应发生。结论:银杏叶片治疗急性缺血性脑卒中疗效好,且用药安全。     

Pharmacokinetics and bioavailability of acyclovir sustained-release tablets in dogs.

The pharmacokinetics and bioavailability of acyclovir sustained-release tablets in dogs were investigated. Blood concentrations of acyclovir were determined by RP-HPLC after a single oral dose of two kinds of acyclovir tablets given separately to 6 beagle dogs. The main pharmacokinetics parameters of the acyclovir sustained-release tablet were as follows: T1/2, Tmax and Cmax were 4.10 +/- 0.20 h, 4.05 +/- 0.54 h and 6.90 +/- 0.68 [microg x ml(-1), respectively. MRT was 9.02 +/- 0.44 h. Using acyclovir standard tablet as control, relative bioavailability of the acyclovir sustained-release tablet was 152.2 +/- 49.90%. According to the two-tailed t-test, there was a distinct difference in the data for Tmax, Cmax and AUC between acyclovir sustained-release tablets and acyclovir standard tablets, and the absorbability of acyclovir sustained-release tablets was much better than that of the acyclovir standard tablets.     

辛伐他汀缓释片在比格犬体内的药动学及生物等效性研究

目的:研究辛伐他汀缓释片在比格犬体内的药动学和生物等效性。方法:将6只比格犬随机分成2组,分别单剂量灌服20 mg辛伐他汀缓释片(受试制剂)和市售辛伐他汀片(参比制剂),不同时间采集血样,采用液相- 质谱- 质谱联用法测定比格犬体内的血药浓度并计算药动学参数。结果:参比制剂与受试制剂的C_(max)分别为(23.461±6.043)、(13.942±3.236)ng.mL~(-1);t_(max)分别为(2.158±0.396)、(4.116±1.145 3)h;t_(1/2) 分别为(4.564±0.645)、(8.143±0.679)h;AUC_(0～24 h) 分别为(118.647±31.989)、(129.977±29.853)ng.h.mL~(-1)。结论:受试制剂与参比制剂在吸收速率方面具有显著差异,二者不具有生物等效性。     

兰索拉唑肠溶片体内外相关性研究

目的考察兰索拉唑肠溶片的体外释放与在beagle犬体内吸收间的相关性。方法利用紫外分光光度法测定肠溶片体外释放度;利用高效液相色谱法测定beagle犬口服给药后的体内血药浓度;以Wagner-Nelson法计算其体内吸收分数,考察体内吸收与体外释放的相关性。结果兰索拉唑肠溶片的体内吸收分数fa与体外释放速率ft的关系为:fa=0.812 2ft–9.874 6,r=0.956 8。结论兰索拉唑肠溶片的体外释放与在犬体内吸收相关性良好。     

消炎汤调节肠道微生态改善大鼠慢性盆腔炎的研究

目的探讨消炎汤通过调节肠道微生态的变化对慢性盆腔炎大鼠的治疗作用。方法采用子宫内注射苯酚胶浆建立大鼠慢性盆腔炎模型,造模2周后ig消炎汤5、10、20 g/kg,连续14 d,观察大鼠子宫内膜形态,qPCR检测子宫组织中细胞间黏附分子(ICAM-1mRNA)表达情况,并采用16SrRNA高通道测序观察慢性盆腔炎大鼠肠道菌群的构成和比例。结果各给药组中充血水肿现象少见,且炎症浸润程度好于妇科千金片组。与模型组相比,消炎汤各剂量组子宫组织中ICAM-1mRNA的表达均有下调,尤以消炎汤20 g/kg组为甚(P0.01)。与模型组相比,消炎汤20 g/kg组Simpson指数显著上升(P0.05)。给予消炎汤治疗后肠道菌群多样性、丰度均得到一定程度改善,但未见统计学差异。与模型组相比,消炎汤10、20g/kg组乳杆菌、梭状芽孢杆菌OUT比例有不同程度升高。治疗后,消炎汤20、10g/kg组OUT比例较模型组明显下降。结论消炎汤能够明显改善慢性盆腔炎大鼠子宫的炎症程度,有效减少黏连的发生,作用机制与其调节肠道微生态影响雌激素代谢有关。     

Bioavailability of metronidazole from sugar-coated tablets in humans. II. Evaluation of beagle dogs as an animal model

The bioavailability of metronidazole from five sugar-coated tablets exhibiting different dissolution behaviors relative to pH was determined in beagle dogs, and compared with that in humans administered the same preparations. The gastric pH of beagle dogs, which was determined after collecting the gastric fluid through a catheter inserted into the stomach, ranged in pH from 1.8 to 7.8. From statistical analysis of C_max and AUC_0–24, it was concluded that gastric acidity definitely affects the bioavailability of metronidazole from sugar-coated tablets. The relative values of C_max and AUC_0–24, compared with those of the tablet exhibiting the highest values, ranked similarly between corresponding gastric acidity groups of beagle dogs and humans. A significant correlation was shown between AUC_0–24 for beagle dogs and humans having low gastric acidity (P < 0.05). These results suggest the possibility that beagle dogs may be used as an animal model for testing the bioavailability of a drug preparation showing gastric acidity-dependent bioavailability in humans.     

Preparation and in vitro evaluation of enteric-coated tablets of rosiglitazone sodium

The aim of this study was to prepare the rosiglitazone sodium enteric-coated tablets and investigate its release rate. The rosiglitazone sodium enteric-coated tablet was prepared by single punch tablet press using substituted hydroxypropyl cellulose and polyvinylpyrrolidone (PVP). The release rate from the enteric-coated tablet of rosiglitazone sodium was evaluated. The release rate study showed that few rosiglitazone sodium was released from enteric coated formulation within 2 h in simulated gastric juice, while it released more than 80% of the labeled amount in 30 min in simulated intestinal juice. The preparing method of rosiglitazone sodium enteric-coated tablets was simple and had a good reproducibility. The release condition and determined methods could be used for the routine determinations of rosiglitazone sodium enteric-coated tablets.