琥珀酸美托洛尔缓释片在中国人体的药动学特性

目的研究琥珀酸美托洛尔缓释片在中国人体的药动学特性.方法采用HPLC荧光检测法测定血浆中美托洛尔的浓度.结果22名健康受试者口服单剂量50mg琥珀酸美托洛尔缓释片后的AUC0-t为(173.15±99.52)μg·h·L-1,AUC0-∞为(237.44±162.11)μg·h·L-1,cmax为(15.67±7.69)μg·L-1,tmax为(6.14±2.55)h,MRT为(14.17±4.01)h;多剂量口服50mg缓释片后的AUCss0-t为(335.42±235.19)μg·h·L-1,cmax为(23.03±15.16)μg·L-1,tmax为(5.8±2.2)h,cmin(6.73±4.98)μg·L-1,平均稳态血药浓度cav是(13.98±9.80)μg·L-1,血药浓度波动度DF(%)(122.55±53.93)%.结论单剂量给予缓释片的结果与美托洛尔普通片相比,tmax明显延长(5.8vs 1.1 h),cmax明显降低(15.67×2vs 186.2μg·L-1).琥珀酸美托洛片缓释片与普通片相比在中国健康受试者中的缓释特征明显,安全性良好.在整个试验过程中监测血压、心率,无低血压、血晕等不良反应发生.     

盐酸黄连素对肾移植受者环孢素A增效作用的临床药代动力学研究

目的研究盐酸黄连素对肾移植受者使用环孢素A增效作用的体内动力学过程.方法选择肾移植术后1个月以内、连续服用环孢素A 2周、肝肾功能稳定的患者6名,环孢素A剂量6mg.kg-1·d-1,用FPIA方法(单抗)检测合用黄连素前后各时间点环孢素A全血浓度.结果单服环孢素A的主要药代动力学参数分别为tmax(h)1.33±0.52,Cmax(μg·L-1)1224.75±296 20,Cmin(μg·L-1)173.95±78.71,t1/2(h)2.62±1.00,AUC μg·h·L-14681.34±1300.45,CL/F(L·h-1)35±15;与黄连素合用的主要药代动力学参数为tmax(h)3.00±1.26,Cmax(μg·L-1)1050.10±290.86,Cmin(μg·L-1)321.31±161.29,t1/2(h)5.33±2.60,AUCμg·h·L-16265.71±1 871.33,CL/F(L·     

缓释醋酸亮丙瑞林微球对大鼠子宫异位内膜的抑制作用

目的观察国内研制的醋酸亮丙瑞林(LE)微球对异位子宫内膜的抑制作用,并与进口醋酸亮丙瑞林微球(enanton)及醋酸亮丙瑞林(LE)注射溶液进行疗效比较.方法以手术方法制备大鼠子宫内膜异位症模型,将动物分为辅料组、原料药组(LE,20μg·kg-1·d-1×28d,sc)、进口微球组(enanton20μg·kg-1·d-1,sc)、国产微球组(国产LE微球2、20、200μg·kg-1·d-1,sc).结果辅料组异位内膜体积呈增长趋势,阳性对照药LE20μg·kg-1(sc×28d)、enanton20μg·kg-1·d-1,及国产LE微球2、20、200μg·kg-1·d-1对异位内膜均有明显抑制作用,且后者具有一定的剂量相关性.结论国产醋酸亮丙瑞林微球20μg·kg-1·     

环丙沙星对苯妥英钠药动学的影响

目的研究环丙沙星对苯妥英血药浓度及药动学参数的影响.方法应用紫外分光光度法测定家兔喂服环丙沙星(25 mg·kg-1)前及1周后单剂量静注苯妥英钠(10 mg·kg-1)的经时血药浓度,以"3P87"药动学程序拟合药动学参数.结果合用环丙沙星后,苯妥英血药浓度明显下降(P<0.05), AUC由合并用药前(6639.0±893.9) mg·L-1·min-1降为(4200.7±874.4) mg·L-1·     

国产和进口缬沙坦胶囊的人体生物利用度

目的研究国产和进口缬沙坦胶囊的相对生物利用度.方法22名健康受试者随机、自身交叉服用单剂量的缬沙坦160 mg,用HPLC法测定血浆中的药物浓度,梯形法计算药时曲线下面积,并对主要参数进行统计学分析.结果国产制剂与进口制剂的主要药动学参数 Cmax为(2.1±0.6),(2.1±0.8) μg·ml-1;Tmax为(2.3±0.5),(2.4±0.6) h;AUC0～24为(10.5±3.2),(10.8±3.5) μg·ml-1·h-1;AUC0～∞为(11.7±3.4),(12.0±3.5) μg·ml-1·     

甲硫氨酸脑啡肽对系统性红斑狼疮患者外周血淋巴细胞增殖反应的影响及阿片受体介导机制的研究

目的研究甲硫氨酸脑啡肽(Met-Enk)对系统性红斑狼疮(SLE) 患者外周血淋巴细胞(PBL)增殖反应的影响以及纳络酮(Nal)对其影响的作用.方法淋巴细胞增殖法.结果 Met-Enk(1×10-8～1×10 -6 mol·L-1)能够促进正常人PBL增殖反应,Nal(1×10-6 mol·L-1) 对正常人PBL增殖反应无明显影响,但可拮抗Met-Enk(1×10-6 mol·L-1)对正常人PBL增殖反应的促进作用;Nal(1×10-6 mol·L-1)不仅可拮抗Met-Enk (1×10-6 mol·     

胆道手术病人中头孢曲松钠的药动学

目的研究头孢曲松钠(CTRX)在6例施各类胆道手术附胆总管引流患者的药动学.方法采用微生物学的方法测定血清及胆汁中头孢曲松钠浓度.结果静滴头孢曲松钠3g或2g即刻血药浓度分别可达到(470.9±23.4)μg·ml-1和(288.1±14.3)μg·ml-1,8h后仍保持(91.7±5.1)μg·ml-1和(54.6±4.2)μg·ml-1;T型管胆汁药物峰浓度可达到(1645.81±201.3)μg·ml-1和(1123.8±140.4)μg·     

国产左甲状腺素钠片剂生物利用度研究

目的采用开放随机原则对国产的两种规格(50μg和100μg)的左甲状腺素钠片与进口左甲状腺素钠片进行相对生物利用度及等效性检验研究,旨在观察片剂质量,为临床应用提供依据.方法21名健康男性受试者参加了单剂量(600μg)三周期交叉试验并用放免分析法测定给药后不同时间点血清药物浓度.结果试验药AUC0-t分别为10.13±1.84μmo1·h-1.L-1和10.30±1.42μmo1·h-1·L-1,参比药AUC0-t为9.37±1.27μmo1·h-1·L-1;试验药Cmax分别为197.57±27.40 nmol.L-1和191.10±27.35nmo1·L-1,参比药Cmax为169.48±22.83 nmo1·     

环丙沙星缓释微粒溶出度与兔眼内的药动学

目的研究环丙沙星(CPFX)缓释微粒是否具有缓释长效作用.方法应用HPLC法测定CPFX微粒体外溶出度和在兔眼内释放的药物浓度.结果CPFX微粒在体外72h内累积释放率为86%,K=0.0524.在兔眼内药动学参数为T1/2(Ka)为9.115h,T1/2(ke)为10.55h,Tmax为18.08h,Cmax为1.28μg·ml-1,AUC为57.46μg·h·     

母乳中甲硝唑、替硝唑药动学及产妇合理哺乳时间

目的确定产后静滴甲硝唑及替硝唑乳妇合理的哺乳时间,避免乳汁中药物对婴儿的不良反应.方法采用高效液相色谱法测定乳汁药物浓度,并计算其药动学参数.结果哺乳妇女单剂量静滴甲硝唑(20mg·kg-1,n=8)﹑、替硝唑(13mg·kg-1,n=7)乳汁中药动学参数达峰时(Tmax)、峰浓度(Cmax)、消除半衰期(T1/2ke)分别是(1.7±1.0)h,(20.1±5.0)μg·ml-1,(6.4±3.3)h和(1.3±0.6)h,(17.2±3.1)μg·ml-1,(11.0±3.5)h.结论静滴甲硝唑(20mg·kg-1)的乳妇宜于给药后3～4h哺乳;静滴替硝唑(13mg·     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.