Quinacrine不同给药途径对家兔血药浓度的影响

目的　研究 quinacrine经不同途径给药的血药浓度 ,了解 quinacrine经阴道向子宫内给药绝育 (quinacrine女性非外科绝育法 )可能产生的毒副反应。方法　以兔为模拟对象 ,用荧光分析法分别测定宫腔内缓释给药、静脉、口服和输卵管内注射等 4种不同途径给quinacrine的血药浓度变化。结果　血药浓度峰值以静脉给药法最高 ,宫腔内缓释给药法最低。宫腔内缓释给药法的血药浓度水平接近其他给药方法血药浓度水平的残余浓度。血药浓度下降的起点静脉法在给药后立即产生 ,口服法在给药后 8h出现 ,输卵管内注射法见于给药后 4h ,而宫内缓释法则可维持到 7d。结论　从是否产生全身性的毒副反应的角度看 ,quinacrine宫腔内缓释给药法比口服法低 ,用于女性非外科手术绝育是安全的     

美施康定阴道给药治疗重度癌痛32例疗效观察

目的：观察美施康定（MST)阴道给药治疗晚期癌症疼痛的止痛效果。方法：对口服MST引起顽固性恶心、呕吐、吞咽困难及便秘等症状的病人改为阴道给药。结果：32例重度癌痛患者经阴道给药后疼痛缓解率达93．8％，且由口服给药改为阴道给药无需增加剂量，生活质量明显提高，不良反应与口服给药基本相同，主要为便秘、恶心、呕吐等。结论：MST阴道给药具有良好的镇痛效果，对不能口服给药的晚期癌症患者是安全、有效的止痛方法。     

米索前列醇阴道置药的新进展

米索前列醇 (简称米索) 是一种合成的前列腺素 E1 衍生物, 临床研究表明口服给药经肝脏代谢, 半衰期短, 用药次数多,不良反应发生率高。阴道给药,经阴道粘膜吸收,直接作用于靶器官,作用时间长,克服了胃肠道不良反应的发生[1 ]。现将其阴道用药作一综述。1 终止早孕1.1 联合应用     

抗早孕新药RU486的药理研究

RU 486经口服、皮下、肌肉和阴道四种途径给药,对大鼠有显著的抗早孕作用;幼兔子宫内膜增生试验证明其在大剂量时有明显的抗孕酮活性;大鼠子宫体外孕激素胞浆受体结合力试验证明与孕酮受体有很强的结合能力。此外还进行了血浆药物半衰期及急性毒性测定。     

米索前列醇凝胶剂抗早孕作用研究

目的了解米索前列醇新剂型—凝胶剂,对大鼠在体子宫平滑肌的收缩频率、幅度的影响,为制药企业开发和临床应用米索前列醇凝胶剂提供客观依据。方法采用抗早孕的动物研究方法,将米索前列醇凝胶剂通过大鼠阴道给药,进行药物作用实验。结果米索前列醇通过阴道给药可明显增强大鼠子宫收缩力,并且较口服给药起效时间缩短。结论米索前列醇凝胶剂是抗早孕的一种较好的剂型。     

消糜阴道泡腾片联合甲硝唑片治疗细菌性阴道病50例

细菌性阴道病与宫颈上皮非典型增生、宫内膜炎、输卵管炎、盆腔炎、泌尿系统感染有关,也可导致不孕、异位妊娠、产褥感染、新生儿感染。目前该病的治疗药物有多种,最有效的药物是甲硝唑,可静脉给药、口服给药及阴道给药。甲硝唑口服给药及阴道给药治疗细菌性阴道病均有明显的疗效,阴道给药效果略优于口服给药。     

吡硫翁锌乳膏对银屑病样模型小鼠的药效学研究

目的：研究吡硫翁锌乳膏抗银屑病的作用。方法：采用小鼠雌激素期的阴道上皮模型和鼠尾鳞片表皮银屑病样皮损模型,观察吡硫翁锌乳膏抗银屑病的作用。在小鼠雌激素期的阴道上皮模型中,吡硫翁锌乳膏经小鼠阴道给药,连续给药14 d,观察小鼠阴道上皮分裂指数的变化。在鼠尾磷片表皮银屑病样皮损模型中,吡硫翁锌乳膏被涂抹于小鼠尾部,连续给药14 d,观察鼠尾含有颗粒层的鳞片数目的变化,及对小鼠上皮细胞有丝分裂及表皮细胞分化的影响。结果：经吡硫翁锌乳膏处理后,小鼠阴道上皮分裂指数明显降低,鼠尾含有颗粒层的鳞片数目明显增加。结论：吡硫翁锌乳膏能明显抑制阴道上皮细胞分裂,促进尾鳞片表皮颗粒层形成,具有潜在的抗银屑病样的作用。     

脑脉通胶囊药理作用实验研究

脑爱胶囊口服给药,具有显著增另狗脑血流量、降低脑血管阻力作用,作用是量效关系。大鼠灌胃给经,具有显著抗血小板聚集作用及抗血栓形成作用,作用是量效关系。     

米索前列醇宫颈管与直肠序贯给药用于流产的临床观察

米非司酮配伍米索前列醇用于药物流产的效果临床上已得到肯定,各种给药途径的完全流产率差异无显著性,因局部给药较口服给药具有血药浓度稳定、作用时间长等特点,因此,大多数研究者推荐阴道给药这一途径[1].我院采用口服给药及口服配伍宫颈管与直肠序贯给药两种给药途径用于流产,旨在探讨一种更为合理的给药方法.     

不同途径应用雌激素对围绝经期综合征的疗效

目的　探讨不同途径给予结合型雌激素对围绝经期妇女子宫内膜厚度、阴道细胞学及更年期症状的影响。方法　 48例围绝经期妇女随机分为两组 ,口服给药组 2 4例 ,阴道给药组 2 4例 ,分别口服及阴道给予倍美力片剂 0 62 5mg ,比较两组用药前后子宫内膜厚度和阴道细胞学评分的变化及症状改善程度。结果　用药后口服给药组内膜厚度有显著改变 (P <0 0 1) ,而阴道细胞学评分改变不显著 ;阴道给药组内膜厚度无明显改变 ,而阴道细胞学评分较用药前明显提高 (P <0 0 1)。结论　围绝经期妇女全身症状以口服补充雌激素为佳 ,局部症状以阴道给药为佳     

Vaginal misoprostol for induction of labour: a more effective agent than prostaglandin F2 alpha gel and prostaglandin E2 pessary

OBJECTIVES: To compare labour outcome in women who had labour induced with PGF2 alpha gel, PGE2 vaginal pessary or misoprostol administered intravaginally or orally. STUDY DESIGN: Unmasked randomised controlled trial. SETTING: Department of Obstetrics and Gynaecology, University of Zimbabwe, Harare. SUBJECTS: Women with a singleton foetus in cephalic presentation after 37 weeks gestation admitted for induction of labour who were randomised to prostaglandin F2 alpha gel (n = 76), prostaglandin E2 pessary (n = 75) and misoprostol administered either intra-vaginally (n = 128) or orally (n = 127). MAIN OUTCOME MEASURES: Primary outcome was induction to delivery interval. Secondary outcomes included use of oxytocin during labour, mode of delivery, duration of labour, neonatal condition at delivery and maternal complications. METHODS: Four hundred and six women admitted for induction of labour with a singleton foetus in cephalic presentation after 37 weeks gestation were enrolled. To estimate the risk with induction using other agents the odds ratio and 95% confidence interval was calculated using the group that received prostaglandin F2 alpha gel as referents. RESULTS: The women were comparable for baseline characteristics. Compared to prostaglandin F2 alpha gel, the need for augmentation with oxytocin in labour was significantly reduced in women induced with prostaglandin E2 pessary (OR 0.46; 95%CI 0.23 to 0.93), vaginal misoprostol (OR 0.34; 95%CI 0.18 to 0.63) and oral misoprostol (OR 0.42; 95%CI 0.22 to 0.78). There was no difference in mode of delivery. There was a significantly reduced risk (OR 0.20; 95%CI 0.04 to 0.86) of Caesarean section (CS) for failure to progress in the vaginal misoprostol group. Labour induced with misoprostol and prostaglandin E2 pessary was significantly shorter than in prostaglandin F2 alpha gel. Vaginal misoprostol significantly shortened the induction to delivery interval. There were more admissions to the neonatal unit in the misoprostol groups. CONCLUSION: Compared to prostaglandin F2 alpha gel, misoprostol and prostaglandin E2 pessary had reduced need for oxytocin and a shorter duration of labour. Effects of misoprostol on the foetus need further investigation before it is used as a routine agent for induction of labour.     

甜梦口服液与丁螺环酮治疗广泛性焦虑症的疗效对比

目的观察甜梦口服液治疗广泛性焦虑症的临床疗效和药物不良反应。方法选择90例患者按照随机数字表法分为甜梦口服液组45例、丁螺环酮组45例，疗程均为6周，比较2组治疗前后汉密尔顿焦虑量表（HAMA）、焦虑自评量表（SAS）评分、临床疗效总评量表及药物不良反应量表。结果治疗6周后，HAMA和SAS评分2组治疗前后均有统计学意义（P〈0．05），但丁螺环酮组与甜梦口服液组治疗后总有效率为86．67％与88．89％，差异无统计学意义（P〉0．05）。甜梦口服液组对改善躯体性焦虑因子评分疗效好于丁螺环酮组，差异具有统计学意义（P〈0．05）。结论甜梦口服液与丁螺环酮对广泛性焦虑障碍的疗效差异无统计学意义，但甜梦口服液药物不良反应少．安全性好．同时明显改善患者躯体不适．提高了生活盾号。     

止咳清肺口服液止咳和化痰作用的实验研究

目的观察止咳清肺口服液的止咳和祛痰作用。方法采用小鼠氨水引咳法观察镇咳作用;采用小鼠酚红排泌法观察化痰作用。结果止咳清肺口服液可显著减少氨水引起小鼠咳嗽的次数,并延长咳嗽潜伏期,明显增加小鼠气管酚红排泌量。结论止咳清肺口服液有显著的止咳和祛痰作用。     

Dose-independent pharmacokinetics of metformin in rats: Hepatic and gastrointestinal first-pass effects

Pharmacokinetic parameters of metformin were evaluated after intravenous and oral administration (50, 100, and 200 mg/kg) in rats. The hepatic, gastric, and intestinal first-pass effects were also measured after intravenous, intraportal, intragastric, and intraduodenal administration (100 mg/kg) in rats. The total area under the plasma concentration-time curve from time zero to time infinity (AUC) values were dose-proportional after both intravenous and oral dose ranges studied. After oral administration (100 mg/kg), approximately 4.39% of oral dose was not absorbed and extent of absolute oral bioavailability (F) value was approximately 29.9%. The gastrointestinal first-pass effect of metformin was approximately 53.8% of oral dose in rats (the gastric and intestinal first-pass effects were approximately 23.1 and 30.7%, respectively), and the hepatic first-pass effect was approximately 27.1% after absorption into the portal vein. Since approximately 41.8% of oral metformin was absorbed into the portal vein, the value of 27.1% is equivalent to 11.3% of oral dose. The first-pass effects of metformin in the lung and heart were almost negligible in rats. The low F value of metformin in rats was mainly due to considerable gastrointestinal first-pass effects. The stability of metformin, distribution of metformin between plasma and blood cells, and factors affecting protein binding of metformin to 4% human serum albumin were also discussed.     

Effect of preoral and transdermal insulin preparations on blood glucose concentration in mice

Effects of oral and transdermal insulin applications on blood glucose concentration were investigated in nonconditioned, healthy mice. Insulin was applied in a special lipid formulation which contained no chemical enhancers or protease inhibitors. In comparison to control applications with same volumes of insulin free lipid formulations significant and reproducible blood sugar lowering effects were found with the insulin-lipid formulation. Additional control applications of the same dosages of oral aqueous insulin solutions differed only slightly to the insulin free lipid formulations. Same dosages of s.c.- and p.o.-applications of the insulin-lipid-formulation induced quantitatively comparable blood sugar lowering effects. The maximum oral effects showed dose dependence in a dose range of 0.7 to 9.5 IU/kg bodyweight. Maximal effects after oral application were seen 1-2 h after oral application. Investigations with transdermal insulin applications showed also significant effects in lowering blood glucose concentrations, but these effects were weaker than after oral application and showed a delayed onset.     

Physiological, subjective and reinforcing effects of oral and intravenous cocaine in humans

RATIONALE: There is little comparative information on the qualitative similarity, relative potency and reinforcing effects of oral cocaine versus cocaine administered via other routes. METHODS: The present study used a within-subject, double-blind, double-dummy design to compare the physiological, subjective and reinforcing effects of placebo and oral (62.5, 125, 250 mg/70 kg) and intravenous (IV) (12.5, 25, 50 mg/70 kg) cocaine in volunteers with histories of cocaine abuse. RESULTS: Cocaine produced dose-dependent increases on heart rate and blood pressure, with effects lasting longer after oral than IV cocaine. Subjective ratings (e.g., "rush," "drug effect," "liking") were qualitatively similar and dose-dependently increased after oral and IV administration, and the duration of effects was similar under both routes. On a money versus drug choice measure of reinforcement, the monetary amounts at which participants chose drug over money increased as a function of cocaine dose under both routes of administration. At doses that produced comparable subjective, physiological, and reinforcing effects, oral cocaine was not identified as cocaine as frequently as IV cocaine. Across measures, the data suggested that IV cocaine was approximately 10 times more potent than oral cocaine. CONCLUSIONS: Overall, the results of this study support qualitatively similar effects of oral and IV cocaine and suggest that oral cocaine may be an effective tool for studying cocaine's effects in human laboratory studies.     

不同比例五味子宁神口服液镇静催眠作用研究

目的:寻找五味子宁神口服液镇静催眠作用的最佳配伍比例。方法:通过对小鼠自发活动的影响、对戊巴比妥钠的协同作用、对中枢神经递质的影响等3方面药理学研究,探讨五味子宁神口服液不同配伍比例的镇静催眠作用。结果:五味子宁神口服液以原方用药25%五味子比例作用最好。结论:五味子宁神口服液组方配伍是合理的。     

扁咽口服液抗炎及其对急性咽炎模型大鼠治疗作用的实验研究

目的观察评价扁咽口服液的抗炎作用,并考察其对急性咽炎的治疗作用和对常见呼吸道病原菌的抑菌活性。方法运用小鼠耳廓肿胀实验、大鼠足肿胀实验和小鼠腹腔白细胞游走实验,评价扁咽口服液的抗炎作用;并采用大鼠急性咽炎模型,观察扁咽口服液的治疗作用;采用平皿法测定扁咽口服液对常见呼吸道病原菌的最低抑菌浓度。结果扁咽口服液可显著降低二甲苯引起的小鼠耳廓肿胀度,减轻角叉菜胶所致大鼠的足肿胀(P<0.05或P<0.01);扁咽口服液高、中剂量显著降低羧甲基纤维素钠致小鼠腹腔白细胞游走(P<0.05);扁咽口服液可减轻急性咽炎模型大鼠咽部黏膜的炎症表现,缓解急性咽炎症状,并且随着药物剂量的增加,其抗炎作用和对咽部黏膜的改善作用均增强。扁咽口服液对金黄色葡萄球菌、肺炎克雷伯菌、大肠杆菌、肺炎链球菌、乙型溶血性链球菌均较为敏感,其最小抑菌浓度分别为56、28、56、28、14 mg/mL。结论扁咽口服液具有良好的抗炎作用,对急性咽炎有明显的疗效。     

Pharmacokinetics and pharmacodynamics of procyclidine in man

The pharmacokinetics and pharmacodynamics of procyclidine (10 mg) after oral and intravenous administration were studied in six healthy volunteers. Treatment order was randomised and the study was placebo-controlled and conducted blind. After oral dosing the mean peak plasma concentration was 116 ng/ml and mean bioavailability was 75%. After both oral and intravenous dosing the mean values for the volume of distribution, total body clearance and plasma elimination half-life of procyclidine were in the order of 1 l/kg, 68 ml/min and 12 h respectively. Autonomic effects were maximal within 0.5 h of intravenous administration and at about 1-2 h after oral dosing. Significant effects on pupil diameter, visual near point, salivary secretion and heart rate occurred after intravenous treatment and similar but less marked effects occurred after the oral dose. Significant autonomic effects were still detectable 12 h after both forms of treatment.     

活血化瘀膜剂的药效实验研究

将临床上具有活血化瘀作用的活血化瘀口服汤剂改制为膜剂,并对其临床治疗指标相关的药效进行了实验,结果显示活血化瘀膜剂与活血化瘀口服汤剂比较,在抗炎、止痛、消血肿及促进毛细血管微循环方面具有相似药效作用,且膜剂作用强于口服汤剂。为活血化瘀汤的剂型改良提供了依据。