注射用丹参多酚酸盐成品输液的稳定性

目的 考察注射用丹参多酚酸盐成品输液稳定性.方法 分别考察室温(25℃)和冷藏(4℃)条件下,注射用丹参多酚酸盐的3种临床常用成品输液在0~8 h间的有效成分的含量、输液外观、pH值及不溶性微粒的数量的变化.结果 注射用丹参多酚酸盐与胰岛素在5%葡萄糖注射液中混合调配后,无论在室温或冷藏条件下,2 h内成品输液丹酚酸B含量下降均超过10%,溶液pH值超过6,≥10μm不溶性微粒的数量超过25个/毫升,≥25μm不溶性微粒的数量超过3个/毫升.使用5%葡萄糖注射液和0.9%氯化钠注射液稀释的成品输液,室温保存8 h稳定.然而,在冷藏条件下,0.9%氯化钠注射液稀释后的成品输液6 h内不溶性微粒数超出规定范围,而5%葡萄糖注射液稀释后的成品输液2 h内不溶性微粒的数量超出规定范围.结论 注射用丹参多酚酸盐不宜与胰岛素配伍使用.在冷藏条件下,建议采用0.9%氯化钠注射液稀释后的成品输液保存不得超过6 h,采用5%葡萄糖注射液稀释后的成品输液保存不得超过2 h.     

大株红景天注射液与不同溶媒配伍的不溶性微粒考察

摘 要 目的： 考察大株红景天注射液在常用的4种溶媒（0.9%氯化钠注射液、5%葡萄糖注射液、果糖注射液、木糖醇氯化钠注射液）中配伍的稳定性。方法: 采用《中国药典》2010年版规定的方法考察大株红景天注射液与4种溶媒配伍后分别在0,0.5,1,2,4,8 h内产生不溶性微粒数量和pH的变化。结果: 在8 h内大株红景天注射液与4种溶媒配伍后的外观及pH无明显变化。在0.9%氯化钠注射液,5%葡萄糖注射液中的不溶性微粒数符合药典规定。0.9%氯化钠注射液中不溶性微粒数量小于5%葡萄糖注射液。在果糖注射液中不溶性微粒数超过药典标准,尤其在4h不溶性微粒数明显增多。在木糖醇氯化钠注射液中不溶性微粒数略高于药典标准。结论:建议大株红景天注射液选用0.9%氯化钠注射液,5%葡萄糖注射液做溶媒。不推荐果糖注射液,木糖醇氯化钠注射液做溶媒。虽然说明书未提及大株红景天注射液用0.9%氯化钠注射液做溶媒。本试验可为糖代谢异常患者用药提供一个参考依据。     

注射用丹参多酚酸盐与12种溶剂的配伍稳定性考察

目的：考察注射用丹参多酚酸盐与临床常用溶剂的配伍稳定性,为临床应用提供参考。方法：模拟临床用药情况,将注射用丹参多酚酸盐与12种常用溶剂配伍,观察配制溶液外观,测定配伍后8h内pH、不溶性微粒和吸光度变化。结果：注射用丹参多酚酸盐与极化液、20％甘露醇注射液、复方氯化钠注射液、木糖醇注射液、右旋糖酐40葡萄糖注射液、5％葡萄糖氯化钠注射液、乳酸钠林格注射液配伍后8h内不溶性微粒超出或接近《中国药典》标准。与碳酸氢钠注射液配伍后溶液pH超出注射用丹参多酚酸盐的厂家质量标准。注射用丹参多酚酸盐与5％葡萄糖注射液、10％葡萄糖注射液、甘油果糖注射液、0．9％氯化钠注射液的配伍液8h内外观、pH、不溶性微粒、吸光度等皆符合规定。结论：注射用丹参多酚酸盐适宜上述4种溶液配伍在8h内基本稳定。     

4种常用中药注射液不同浓度对不溶性微粒的影响

摘 要 目的：考察4 种常用中药注射液与0.9%氯化钠注射液不同浓度配伍的不溶性微粒数变化,为临床选择药物浓度提供参考。方法: 将复方苦参注射液、疏血通注射液、鹿瓜多肽注射液、注射用红花黄色素用0.9%氯化钠注射液制成低浓度和高浓度溶液,按照中国药典2015版第四部通则0903不溶性微粒检查法测定其配伍前与配伍后0,2,4,5 h的不溶性微粒数。结果: 4种中药注射剂原液和0.9%氯化钠注射液不溶性微粒符合要求;4种中药注射剂不同浓度下≥25 μm不溶性微粒数量都很少,几乎不随时间变化;4种中药注射剂≥10 μm不溶性微粒数总体呈现高浓度输液中的微粒数略多于低浓度,随时间变化趋势各不相同。结论:高浓度中药注射剂输液中≥10 μm不溶性微粒数较低浓度中药注射剂输液略多,建议临床按照说明书规定的浓度进行药物稀释,并尽快使用。     

注射用丹参多酚酸盐与21种临床常用药品配伍稳定性研究

目的 考察注射用丹参多酚酸盐与21种临床常用药品配伍后的稳定性.方法 模拟临床用药,将注射用丹参多酚酸盐200mg分别与临床21种常用药品,用0.9%氯化钠注射液250 mL或5%葡萄糖注射液稀释配伍,观察溶液外观,测定配伍后4 h内pH、不溶性微粒和含量的变化.结果 注射用丹参多酚酸盐与维生素C注射液、黄芪注射液、单硝酸异山梨酯注射液、盐酸川芎嗪注射液、地塞米松磷酸钠注射液配伍使用时pH超出注射用丹参多酚酸盐厂家质量标准;与香丹注射液配伍在0.9%氯化钠注射液为溶刺的情况下,含量在1 h后下降.注射用丹参多酚酸盐与其他15种临床常用药品配伍,0～4 h内外观、pH、不溶性微粒、含量测定方面均符合规定.结论 注射用丹参多酚酸盐与所选15种,临床常用药品配伍在4 h内基本稳定.但基于中药注射液成分的复杂性,建议临床上单独使用.     

多因素多水平多指标考察丹参注射液与溶媒配伍的稳定性

摘 要 目的: 考察多因素对丹参注射液与溶媒配伍后稳定性的影响,优选出最佳配伍方案。方法: 选择温度、剂量、放置时间、溶媒、溶媒用量5个影响因素,采用L₁₈(3⁷)正交试验表,用GWF-5J 型微粒分析仪测定溶液中微粒含量,用HPLC法测定溶液中丹参素钠、原儿茶醛、丹酚酸B和迷迭酸含量。结果:配伍温度、放置时间对溶液中丹参素钠、原儿茶醛、丹酚酸B的含量有显著性影响;剂量对溶液中微粒的含量有显著性影响。结论:丹参注射液合理配伍条件为25℃、剂量20 ml、与100 ml 0.9%氯化钠注射配伍放置2h、稳定性较好。     

苦碟子注射液与常用溶媒配伍的稳定性研究

目的:通过考察苦碟子注射液与常用溶媒的配伍变化,指导临床合理使用苦碟子注射液。方法:将苦碟子注射液与常用溶媒(灭菌注射用水、5%葡萄糖注射液、10%葡萄糖注射液、0.9%氯化钠注射液、复方氯化钠注射液)配伍,定时考察配伍后溶液的外观、pH、不溶性微粒及质量浓度变化情况。结果:室温4 h内,配伍后混合液外观及pH均无明显改变;光照对溶液颜色无明显影响;灭菌注射用水、5%葡萄糖注射液、10%葡萄糖注射液、0.9%氯化钠注射液作为溶媒的不溶性微粒数目均符合2010年版《中国药典》规定;与常用溶媒配伍后,只有与10%葡萄糖注射液配伍时,总黄酮质量浓度未见明显变化。结论:10%葡萄糖注射液为苦碟子注射液最佳溶媒。     

注射用艾司奥美拉唑钠配伍稳定性考察

目的 考察注射用艾司奥美拉唑钠与0.9%氯化钠注射液在不同条件下的配伍稳定性。方法 将不同浓度注射用艾司奥美拉唑钠与0.9%氯化钠注射液配伍,然后将配置好的溶液放置于室温、遮光、光照（4 500 Lx）、40℃恒温环境下,定时考察注射用艾司奥美拉唑钠的性状、pH值、不溶性微粒数和艾司奥美拉唑的含量。结果 注射用艾司奥美拉唑钠在放置过程中出现不同程度的颜色变化,变化程度：40℃恒温 > 光照 > 室温 > 遮光。在4种条件下成品液pH值均相对稳定,pH值12 h内几乎无变化,24,48 h内略微下降,40℃恒温下降较多。高浓度溶液在40℃恒温条件下于48 h不溶性微粒数超出药典规定,其他所有溶液的不溶性微粒均符合药典要求。48 h内艾司奥美拉唑的含量也有所下降,40℃恒温条件下降较多。结论 注射用艾司奥美拉唑钠在40℃恒温条件下最不稳定,遮光条件下溶液最稳定。因此建议注射用艾司奥美拉唑成品溶液保存在室温条件下,尽量避光,同时避免高温影响,低浓度溶液（0.4 mg·mL^-1）在配置后12 h内使用,高浓度溶液（1.6 mg·mL^-1）8 h内滴完。     

注射用丹参与输液配伍的稳定性考察

目的考察注射用丹参(冻干)与临床常用输液配伍后的稳定性情况.方法模拟临床用药方法,将注射用丹参与0.9%氯化钠注射液、5%葡萄糖注射液配伍,测定配伍后溶液6 h内pH值、不溶性微粒数和丹参素与原儿茶醛的含量.结果注射用丹参与0.9%氯化钠注射液、5%葡萄糖注射液配伍后溶液6 h内pH值变化较小;配伍液不溶性微粒数远远高于原注射液的不溶性微粒数(P<0.01);主要成分丹参素钠和原儿茶醛的含量基本无变化.结论注射用丹参与输液配伍后6 h内质量基本稳定.但配伍后溶液不溶性微粒数比原输液大大增多的现象必须引起重视.     

注射用血栓通正交试验优化调配技术及其在不同溶媒中稳定性考察

目的 为了优化注射用血栓通调配工艺,并考察其与0.9%氯化钠注射液(sodium chloride injection)、葡萄糖氯化钠注射液(glucose and sodium chloride injection)、5%葡萄糖注射液(5% glucose injection)和10%葡萄糖注射液(10% glucose injection)配伍的稳定性。 方法 通过正交试验优化注射用血栓通的调配工艺,测定成品输液的不溶性微粒:pH值及主成分(三七皂苷R1、人参皂苷Rg1,人参皂苷Rb1)的相对含量变化,考察注射用血栓通在不同溶媒中的8 h内的配伍稳定性。 结果 注射用血栓通用注射用水溶解完全。四种溶媒配制的成品输液在存放8 h内pH值以及不溶性微粒较稳定。5%葡萄糖注射液和10%葡萄糖注射液配制的成品输液主要成分呈下降趋势。 结论 注射用血栓通最佳调配工艺为使用灭菌注射用水6 mL作为溶媒注入药品西林瓶中,振荡5 min溶解,振荡频率为1 000 r·min-1;0.9%氯化钠注射液和葡萄糖氯化钠注射液调配的成品输液8 h内稳定;5%葡萄糖注射液调配的成品输液6 h内稳定,10%葡萄糖注射液调配的成品输液建议现用现配。     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Polymorphisms in genes involved in neurotransmission in relation to smoking

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D₁, D₂, and D₄ receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D₃ and D₅ receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.     

Tramadol concentrations in blood and in cerebrospinal fluid in a neonate

Based on blood and cerebrospinal fluid samples collected in a full-term neonate, the penetration of tramadol in the central nervous system is described. Following intravenous administration of tramadol, a lag time of about 4 h was observed until full blood–brain equilibration was achieved. This pharmacokinetic observation is in line with a recent pharmacodynamic evaluation of the central opioid effects of tramadol in adults.     

Disease control in asthmatic children seen in private practice in Switzerland

ABSTRACT

Background: Asthma is the most common chronic childhood disease in Switzerland with a prevalence of 10%. Asthma has a high economic burden accounting for high medical costs. Assessment of disease control is likely to be of help in the implementation of strategies to improve asthma. Therefore, we aimed to evaluate asthma control and therapy regimens among children in private practice.

Methods: We assessed asthma control as well as therapy regimens in 575 asthmatic children in an experience programme in Switzerland by using an abbreviated questionnaire based on the asthma control questionnaire and the child health questionnaire on Visit 1 and Visit 2.

Results: Good asthma control at Visit 1 was only present in 25.7% of asthmatic children. Occasional asthma symptoms, limitation of physical activity, nocturnal awakening and anxiety of the parent was present in 80.5%, 41.2%, 46.8% and 57% of the children, respectively. After adjustment of therapy regimens at Visit 1, mainly by adding a leukotriene receptor antagonist, asthma control was reported to be much better in 53.4% of the children at Visit 2.

Conclusions: As asthma control is inadequately achieved within a major portion of asthmatic children, it is imperative to find measures to improve asthma control and hence, to reduce the burden of disease.