HPLC测定复方新斯的明眼用凝胶中维生素B6的含量和有关物质

目的建立复方新斯的明眼用凝胶中维生素B6与有关物质的含量测定方法。方法采用高效液相色谱法,Eclipse XDB—C18色谱柱（4．6mm×150mm,5μm）。流动相：醋酸三乙胺溶液。检测波长：290nm。结果线性范围为1～50μg·mL^-1,r=0．9999（n=5）。低、中、高三个浓度回收率为（100．59±0．57）％,（100．97±0．38）％,（102．20±0．06）％。结论本方法简便快速、专属性好、重复性好、易操作。     

A New Minimal-Stress Freely-Moving Rat Model for Preclinical Studies on Intranasal Administration of CNS Drugs

Purpose  To develop a new minimal-stress model for intranasal administration in freely moving rats and to evaluate in this model the brain distribution of acetaminophen following intranasal versus intravenous administration. Methods  Male Wistar rats received one intranasal cannula, an intra-cerebral microdialysis probe, and two blood cannulas for drug administration and serial blood sampling respectively. To evaluate this novel model, the following experiments were conducted. 1) Evans Blue was administered to verify the selectivity of intranasal exposure. 2) During a 1 min infusion 10, 20, or 40 μl saline was administered intranasally or 250 μl intravenously. Corticosterone plasma concentrations over time were compared as biomarkers for stress. 3) 200 μg of the model drug acetaminophen was given in identical setup and plasma, and brain pharmacokinetics were determined. Results  In 96% of the rats, only the targeted nasal cavity was deeply colored. Corticosterone plasma concentrations were not influenced, neither by route nor volume of administration. Pharmacokinetics of acetaminophen were identical after intravenous and intranasal administration, although the Cmax in microdialysates was reached a little earlier following intravenous administration. Conclusion  A new minimal-stress model for intranasal administration in freely moving rats has been successfully developed and allows direct comparison with intravenous administration.     

氨酚羟考酮胶囊超前镇痛用于后路椎间盘镜局麻手术的临床观察

目的：评价氨酚羟考酮超前镇痛对腰椎局麻手术效果的影响。方法：选择50例有手术适应证的腰椎间盘突出患者,ASAⅠ~Ⅱ级。随机分为2组,各25例,每组均用罗哌卡因100 mg和20 mL利多卡因作局部麻醉浸润,各组局麻药均不加肾上腺素,显露神经根后用1 mL利多卡因原液进行神经阻滞。A组：试验组,术前90 min口服氨酚羟考酮胶囊2粒;B组:对照组,术前30 min肌肉注射杜冷丁80 mg。记录围手术期各时间点的视觉疼痛评分(VAS评分)、手术时间、不良反应发生率。结果：各特定时间点的平均疼痛评分(VAS),A组低于B组,切皮时和摘除突出髓核时两者差异无统计学意义,显露神经根时、关闭切口时,和术后两h的VAS差异有统计学意义（P<0.05),不良反应头痛（P=0.552）、头晕（P=0.031）、嗜睡（P=0.221）和恶心呕吐（P=0.001）的发生率在两组中的差异有统计学意义。结论：氨酚羟考酮超前镇痛效果明显,能够增强效果,延长术后镇痛时间,不良反应发生率低,为超前镇痛提供了新的选择。     

Hepatic injury induces contrasting response in liver and kidney to chemicals that are metabolically activated: role of male sex hormone

Injury to liver, resulting in loss of its normal physiological/biochemical functions, may adversely affect a secondary organ. We examined the response of the liver and kidney to chemical substances that require metabolic activation for their toxicities in mice with a preceding liver injury. Carbon tetrachloride treatment 24 h prior to a challenging dose of carbon tetrachloride or acetaminophen decreased the resulting hepatotoxicity both in male and female mice as determined by histopathological examination and increases in serum enzyme activities. In contrast, the renal toxicity of the challenging toxicants was elevated markedly in male, but not in female mice. Partial hepatectomy also induced similar changes in the hepatotoxicity and nephrotoxicity of a challenging toxicant, suggesting that the contrasting response of male liver and kidney was associated with the reduction of the hepatic metabolizing capacity. Carbon tetrachloride pretreatment or partial hepatectomy decreased the hepatic xenobiotic-metabolizing enzyme activities in both sexes but elevated the renal p-nitrophenol hydroxylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase activities significantly only in male mice. Increases in Cyp2e1 and Cyp2b expression were also evident in male kidney. Castration of males or testosterone administration to females diminished the sex-related differences in the renal response to an acute liver injury. The results indicate that reduction of the hepatic metabolizing capacity induced by liver injury may render secondary target organs susceptible to chemical substances activated in these organs. This effect may be sex-specific. It is also suggested that an integrated approach should be taken for proper assessment of chemical hazards.     

Rectal acetaminophen does not reduce morphine consumption after major surgery in young infants

BACKGROUND: The safety and value of acetaminophen (paracetamol) in additionto continuous morphine infusion has never been studied in newbornsand young infants. We investigated the addition of acetaminophento evaluate whether it decreased morphine consumption in thisage group after major thoracic (non-cardiac) or abdominal surgery. METHODS: A randomized controlled trial was performed in 71 patients giveneither acetaminophen 90–100 mg kg^–1 day^–1orplacebo rectally, in addition to a morphine loading dose of100 µg kg^–1 and 5–10 µg kg^–1h^–1 continuous infusion. Analgesic efficacy was assessedusing Visual Analogue Scale (VAS) and COMFORT scores. Extramorphine was administered if VAS was 4. RESULTS: We analysed data of 54 patients, of whom 29 received acetaminophenand 25 received placebo. Median (25–75th percentile) agewas 0 (0–2) months. Additional morphine bolus requirementsand increases in continuous morphine infusion were similar inboth groups (P = 0.366 and P = 0.06, respectively). There wasno significant difference in total morphine consumption, respectively,7.91 (6.59–14.02) and 7.19 (5.45–12.06) µg kg^–1 h^–1for the acetaminophen and placebo group (P = 0.60). COMFORT[median (25–75th percentile) acetaminophen 10 (9–12)and placebo 11 (9–13)] and VAS [median (25–75thpercentile) acetaminophen 0.0 (0.0–0.2) and placebo 0.0(0.0–0.3)] scores did not differ between acetaminophenand placebo group (P = 0.06 and P = 0.73, respectively). CONCLUSIONS: Acetaminophen, as an adjuvant to continuous morphine infusion,does not have an additional analgesic effect and should notbe considered as standard of care in young infants, 0–2months of age, after major thoracic (non-cardiac) or abdominalsurgery.     

Pharmacotherapy of fever control among hospitalized adult patients

Introduction: Fever is common and associated with increased mortality among hospitalized adults. This article will review the pharmacotherapy of commonly prescribed antipyretic drugs including the rationale for and against temperature control in febrile adults, as well as the evidence associated with fever control in specific patient populations.

Areas covered: Though fever is common, the molecular basis of pyrexia, and the interaction of these pathways with commonly prescribed antipyretic drugs are not fully understood. Furthermore, while experimental and clinical studies clearly demonstrate that pyrexia is harmful in select patients, available clinical trial data are unable to suggest an evidence-based approach to the treatment of fever. Interestingly, this also applies to patients with an acute neurologic injury wherein the treatment of fever with antipyretic therapy has become a common management strategy.

Expert opinion: Few adequately powered clinical trials have investigated temperature control strategies in febrile patients. Therefore, it is not possible to define an evidence-based approach to the control of fever in hospitalized adults. Further clinical and translational research is required to identify the patients most likely to benefit from a strategy of fever control versus permissive hyperthermia, and to determine the antipyretic therapies associated with the greatest improvement in outcome.     

小儿用扑热息痛滴剂的相对生物利用度

作者对１２名健康男性志愿者中进行了两种扑热息痛滴剂的药物动力学比较研究。交叉试验设计，ｐｏ给药量１０００ｍｇ，用高效液相色诺法测定扑热息痛的血药浓度。结果表明，两种滴剂在吸收、分布、代谢上都无显著差异。中美上海施贵宝制药有限公司生产的扑热息痛滴剂的相对生物利用度为上海黄山制药厂的一滴精滴剂的１１１．８８％，提示两种扑热息痛滴剂的生物利用度相仿。     

铜叶绿酸钠对急,慢性肝损伤保护作用的实验研究

以SGPT和SGOT活性升高作为肝损伤指标,证明由蚕沙制得的铜叶绿酸钠(Cu-Chl-Na)对硫代乙酰胺、醋氨酚和四氯化碳所致急性肝损伤均有较好的保护作用。建立了CCl_4皮下注射所致大鼠慢性肝损伤的实验模型,并报道了Cu-Chl-Na对慢性肝损伤的治疗作用。     

Estimation of Agitation Intensity in the GI Tract in Humans and Dogs Based on in Vitro/in Vivo Correlation

In this study, we assessed the hydrodynamic flow around a dosage form in the GI tract in humans by comparing the characteristics of in vitro and in vivo release of two different types of controlled release acetaminophen (paracetamol) tablets, A and B. The former tablet showed an agitation speed-dependent release at a high speed range (50–100 rpm), whereas the latter showed this characteristic at a low speed range (10–50 rpm). The mean release amount-time profiles of tablets A and B in humans showed biphasic characteristics, and the first phase of the absorption profiles of A and B was close to their in vitro profiles at a paddle speed of 10 rpm. The in vivo profiles were also superimposable on in vitro dissolution curves obtained by the flow-through cell method at a flow rate of 1 mL/min (velocity 0.89 cm/min) or less. These results indicate that the hydrodynamic flow around the dosage forms in the human GI tract could be extremely low. The in vivo release rate of these tablets in dogs was greater than in humans, and was estimated to be equivalent to the release rate determined by the paddle method at 100 rpm. This indicates that a higher agitation intensity in the GI tract in dogs than in humans may be one cause of the discrepancies between humans and dogs in drug absorption studies.     

Risks of antipyretics in young children with fever due to infectious disease

The objective of this study was to determine whether paracetamol (acetaminophen) affects the outcome of children with fever due to bacterial infectious disease. A total of 208 outpatients aged 6 months to 15 years with pyrexia due to bacterial infection who had been examined at the Fujimoto Children's Hospital from March 1992 to May 1992. The number of antipyretic doses of paracetamol (10 mg/kg) a day received within 3 days of illness in the patients with acute fever (≥ = 38°C) was investigated. In this study, the patients were divided into two groups: (i) the pneumonia group, which consisted of 101 patients who were subsequently diagnosed as having pneumonia during their illness and (ii) the control group, which consisted of 107 patients who were subsequently diagnosed as having illness with fever that did not progress to pneumonia. The mean number of daily doses was significantly higher for the pneumonia group (2.52 ± 0.80) than for the control group (1.37 ± 0.72, P < 0.001). There was no significant difference between the pneumonia group and the control group in body temperature during acute fever (38.7 ± 0.65 vs 38.8 ± 0.54°C). The data suggest that frequent administration of antipyretics to children with infectious disease may lead to a worsening of their illness.