头孢匹胺钠与甲硝唑的配伍稳定性研究

目的 研究注射用头孢匹胺钠与甲硝唑注射液的配伍稳定性。方法 考察配伍前后溶液外观、不溶性微粒和pH值的变化情况;采用HPLC考察注射用头孢匹胺钠与甲硝唑注射液配伍后,在5,25,35℃,避光、室内光照、紫外线照射条件下,8 h内配伍液中头孢匹胺钠与甲硝唑的含量变化,并考察头孢匹胺钠与甲硝唑在配伍液中有关物质的限度。结果 在混合4 h内,头孢匹胺钠与甲硝唑含量没有明显变化,紫外线对配伍液的稳定性有一定的影响。结论 注射用头孢匹胺钠与甲硝唑注射液在4 h内可配伍使用,应尽量避免日光照射。     

注射用红花黄色素与7种输液的配伍稳定性考察

摘 要 目的：考察注射用红花黄色素与果糖注射液,转化糖注射液,转化糖电解质注射液,葡糖糖氯化钠注射液,5%葡萄糖注射液,10%葡萄糖注射液及0.9%氯化钠注射液配伍的稳定性考察。方法: 模拟临床用药浓度,在室温（25±1）℃下放置8 h,以氯化钠配伍液为对照组,分别观察各种配伍液外观,不溶性微粒数量及pH变化,运用高效液相色谱法测定注射用红花黄色素在不同配伍液中的含量变化。结果:注射用红花黄色素与7种输液配伍后在8h内外观,pH和含量均无明显变化,不溶性微粒数符合中国药典2015年版规定。结论:注射用红花黄色素与7种输液配伍在8 h内稳定。     

注射用辅酶A、三磷酸腺苷二钠及肌苷注射液配伍稳定性考察

摘 要 目的：考察注射用辅酶A、三磷酸腺苷二钠注射液及肌苷注射液在5%葡萄糖注射液中的配伍稳定性。 方法: 在室温条件下,模拟临床用药方法,配制3种药物与5%葡萄糖注射液的配伍溶液,采用HPLC法测定辅酶A、三磷酸腺苷二钠和肌苷的含量及有关物质变化情况,同时考察配伍溶液的外观、pH和不溶性微粒的变化情况。结果: 室温下4 h内,配伍溶液的外观、pH、不溶性微粒、各药物含量及有关物质均无明显变化;24 h后,配伍溶液出现浑浊絮状物,pH、不溶性微粒、含量及有关物质均明显发生变化。结论:在室温条件下,注射用辅酶A、三磷酸腺苷二钠注射液及肌苷注射液在5%葡萄糖注射液中的配伍溶液应于4 h内使用完。     

消癌平注射液与胰岛素在葡萄糖注射液中的配伍稳定性考察

摘 要 目的：考察消癌平注射液与胰岛素在葡萄糖注射液中的配伍稳定性。方法: 观察室温下24h内消癌平注射液与胰岛素在葡萄糖注射液中配伍后溶液外观、不溶性微粒、pH的变化,以及配伍液中绿原酸和胰岛素的含量变化。结果: 配伍液在室温24h内性质稳定、外观、pH无明显变化,无气体沉淀产生、不溶性微粒12h内无明显变化,但24h不溶性微粒数明显升高。主要成分绿原酸及胰岛素的含量均无明显变化。结论: 在该试验条件下,12h内消癌平注射液与胰岛素在5%葡萄糖注射液中配伍稳定。     

肾康注射液与5种溶媒配伍的稳定性考察

摘 要 目的： 通过考察肾康注射液与5种常用溶媒配伍的稳定性,选择最佳溶媒配伍方案,以便临床合理用药。方法: 将肾康注射液与5种不同溶媒配伍后,定时考察配伍后溶液的pH、不溶性微粒数、有效物质原儿茶醛的含量变化情况。结果: 5种溶媒按药品说明书比例配伍2 h后不溶性微粒数均有所增加,其中0.9%氯化钠注射液中的不溶性微粒数最多, 且2 h后不溶性微粒数明显增加。5种配伍溶液的pH无明显变化。原儿茶醛的含量随时间的延长而下降,6 h内原儿茶醛的含量变化率：0.9%氯化钠注射液＞5%果糖注射液＞10%转化糖注射液＞5%葡萄糖注射液＞10%葡萄糖注射液,其中0.9%氯化钠注射液中的原儿茶醛含量下降近20%。结论: 肾康注射液在不同溶媒中稳定性不同,用0.9%的氯化钠注射液配伍的注射液中原儿茶醛含量下降明显且不溶性微粒数较多。临床应选择稳定性更好的葡萄糖以及转化糖注射液作为溶媒,配伍后的溶液应尽可能在2 h内用完。     

正交试验法优选灯盏细辛注射液配伍条件及配伍液的稳定性考察

摘 要 目的： 优选灯盏细辛注射液的配伍条件,并考察配伍液的稳定性。方法: 采用正交试验,以不溶性微粒数量和总黄酮含量为指标性成分,考察温度、溶媒种类、溶媒用量3个影响因素,并对试验结果进行综合分析。按正交试验优选的配伍条件,配制3批样品,24 h内通过外观的观察、溶液不溶性微粒数量、pH以及总黄酮含量的变化来考察灯盏细辛注射液的配伍稳定性。结果: 优选出灯盏细辛注射液最佳配伍条件为：温度25℃、取灯盏细辛注射液2支以0.9%氯化钠注射液250 ml作溶媒。24 h内配伍液的外观、不溶性微粒及pH均无明显变化,4 h内总黄酮的含量也无明显变化,而在4 h后总黄酮的含量有一定程度的下降。结论:在临床用药剂量下,灯盏细辛注射液与0.9%氯化钠注射液250 ml 4 h内可稳定配伍。     

正交试验优选穿琥宁注射液与临床常用输液的配伍条件

目的 研究穿琥宁注射液与临床常用输液的配伍条件。方法 选择温度、光照、放置时间、溶媒种类4个影响因素,以穿琥宁含量、配伍液的pH值变化、不溶性微粒数为检测指标,同时考察不同条件下配伍液中穿琥宁有关物质的限度。结果 在4 h内,穿琥宁注射液与5%葡萄糖注射液及0.9%氯化钠注射液可配伍使用,但不宜与5%的葡萄糖氯化钠注射液配伍。结论 穿琥宁注射液与5%葡萄糖注射液及0.9%氯化钠注射液在4 h内可配伍使用,应尽量避免日光照射与高温环境。     

香丹注射液与乳酸钠林格注射液的配伍稳定性研究

目的 考察香丹注射液与乳酸钠林格注射液配伍的稳定性，为临床安全用药提供参考。方法 按临床用药配伍使用量，制备香丹注射液与乳酸钠林格注射液的配伍溶液，考察配伍溶液的外观、pH值、不溶性微粒、紫外光谱及丹参素钠、原儿茶醛、咖啡酸、紫草酸、丹酚酸B和丹酚酸A的多指标含量。结果 香丹注射液与乳酸钠林格注射液配伍6 h内，溶液性状、pH值、紫外光谱均无显著变化，不溶性微粒呈下降趋势，丹参素钠、原儿茶醛、咖啡酸和丹酚酸B的含量无显著性变化（<3%），紫草酸含量下降了17.41%，丹酚酸A的含量下降了78.64%。结论 香丹注射液与乳酸钠林格注射液在配伍6 h内部分有效成分含量下降，建议减少配伍或配伍后尽快输注，以提高输液的有效性与安全性。     

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。     

依托泊苷、表柔比星与环磷酰胺在输液中的配伍稳定性考察

目的 对依托泊苷、表柔比星与环磷酰胺混合配伍稳定性进行考察,为临床用药安全提供依据。方法 分别考察24 h内25℃常温、25℃避光、4℃冷藏避光条件下3种药物的含量、pH及不溶性微粒的稳定性。结果 3种药物混合溶液的含量、pH值与不溶性微粒在24 h内25℃常温、25℃避光、4℃冷藏避光条件下均未发生明显变化。结论 3种药物的配伍溶液在24 h内稳定性良好,可以为临床用药提供依据。     

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.     

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     

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.     

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.     

Genotoxic effects of chlorophenoxy herbicide diclofop-methyl in mice in vivo and in human lymphocytes in vitro

Diclofop-methyl (DM) is a chlorophenoxy derivative used in large quantities for the control of annual grasses in grain and vegetable crops. In this study, the genotoxic effects of DM were investigated by measuring chromosomal aberrations (CAs) in mouse bone-marrow cells and CA and the comet assay in human peripheral lymphocytes. Mice were treated with 15.63, 31.25, 62.5, and 125?mg/kg body weight of DM intraperitoneally for 24 hours, and 15.63-, 31.25-, 62.5-, 125-, and 250-µg/mL concentrations were applied to human lymphocytes for both 24 and 48 hours. In in vivo treatments, DM significantly, but not dose dependently, increased the total chromosome aberrations, compared to both negative and solvent controls. Cell proliferation was significantly, but not dose dependently, affected by all doses. In in vitro treatments, DM (except 15.63 µg/mL) significantly and dose dependently increased the frequency of chromosome aberrations. Also, 250 µg/mL of 48-hour treatment was found to be toxic. Cell proliferation was significantly and dose dependently affected by DM applications, when compared to negative control. In in vitro treatments, DM significantly decreased the mitotic index only at the highest concentration for 24 hours, and 62.5- and 125-µg/mL concentrations for 48 hours. In the comet assay, a significant and dose-dependent increase in comet-tail intensity was observed at 62.5-, 125-, and 250-µg/mL concentrations. The mean comet-tail length was significantly increased in all concentrations. Our results demonstrate that DM is genotoxic in mammalian cells in vivo and in vitro.     

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.     

2010调脂治疗领域进展

2010年在调脂治疗领域针对他汀治疗心血管病的防治又进行了许多探索。本文通过综述他汀类药物的国际大规模临床试验结果,重新评价了他汀类药物在冠心病一级预防和冠心病二级预防中的地位,阐明了强化他汀治疗的意义;对他汀的心肾保护作用和安全性新证据进行了说明。