简易N-CPAP联合大剂量沐舒坦治疗NRDS的临床研究

目的探讨简易鼻塞式持续呼吸道正压给氧(N-CPAP)联合大剂量沐舒坦治疗新生儿呼吸窘迫综合征(NRDS)的治疗效果。方法对36例NRDS应用简易N-CPAP联合大剂量沐舒坦治疗,并对其临床疗效、不良反应进行分析评估。结果治疗成功34例,失败2例。结论简易鼻塞式持续呼吸道正压给氧(N-CPAP)联合大剂量沐舒坦治疗新生儿呼吸窘迫综合征(NRDS)是基层治疗新生儿呼吸窘迫综合征的最有效的方法,值得推广。     

沐舒坦注射液与常用抗生素配伍禁忌的实验观察

沐舒坦注射液的通用名称为盐酸氨溴索注射液,是一种无色澄明的液体,具有镇咳、祛痰、改善呼吸功能的作用,与抗生素合用有协同作用,我科常将其与抗生素合用治疗小儿呼吸道感染性疾病。在临床应用中,我们发现,沐舒坦注射液与多种药物存在配伍禁忌,有报道显示,沐舒坦注射液与痰热清注射液存在配伍禁忌,不宜配伍。沐舒坦注射液在2006年第5版《新编380种注射液理化与治疗学配伍检索表》中查阅不到。因此,我们将沐舒坦注射液与我科常用的各种抗生素发生反应的情况做了实验观察,现报道如下。     

大剂量沐舒坦在食管癌围手术期中的应用观察

目的探讨大剂量沐舒坦在食管癌围手术期应用中的临床效果。方法80例食管癌患者随机平均分为两组,实验组40例在围手术期使用大剂量沐舒坦治疗,对照组40例使用常规剂量沐舒坦。结果对照组有1例失访;两组病例术后第1天呼吸功能均显著下降至术前的34．3％～42．6％,术后第3、第7、第14天呼吸功能逐渐恢复,最终能达到术前55．5％～82．5％,其中在术后第3及第7天实验组FEV％、第14天对照组VC％恢复优于对照组;肺功能不良事件发生率分别为7．5％（实验组）及10．3％（对照组）,两组差异无统计学意义。结论在食管癌围手术期使用大剂量沐舒坦能够促进术后肺功能恢复。     

大剂量沐舒坦对重症肺炎机械通气患者疗效的分析

目的 研究大剂量沐舒坦对重症肺炎机械通气患者的临床疗效.方法 将2011年1月至2012年12月我院60例20 ～ 65岁收住院的重症肺炎呼吸衰竭需行机械通气患者随机分成对照组及观察组,两组均予常规抗感染及机械通气、对症及支持治疗,对照组用沐舒坦60 mg/天,静脉注射;观察组用沐舒坦20 mg/kg·天,静脉三小时微泵注入;分别观察两组治疗前、治疗5天后、治疗7天后的肺损伤评分、PaO2、PaO2/FiO2、肺顺应性（CL）、气道峰压（PIP）、气道阻力（RAW）,机械通气时间及ICU停留时间、4周存活率.结果 大剂量沐舒坦治疗组患者的PaO2、PaO2/FiO2、肺顺应性（CL）、气道峰压（PIP）、气道阻力（RAW）,机械通气时间、ICU停留时间明显较常规剂量组疗效要好（P＜0.05）;两组存活率无明显差异（P＞0.05）.结论 临床上大剂量沐舒坦的应用对重症肺炎应用机械通气的患者的治疗及预后可能有一定的疗效.     

沐舒坦雾化吸入治疗支气管肺炎的疗效观察及护理对策

目的观察沐舒坦雾化吸入治疗支气管肺炎的疗效并探讨护理对策的临床应用。方法选取支气管肺炎患者74例,进行治疗方法选择、护理措施应用、预防并发症等护理对策。结果经过沐舒坦雾化吸入治疗的实施和临床护理对策的应用,经统计,显效45例(60.81%),总有效率90.54%。结论经过我院医护人员的一致努力,使疾病得到了及时的治疗,控制了病情的发展,减少了并发症的发生,提高了患者的生活质量,实践证明,沐舒坦雾化吸入对支气管肺炎治疗效果显著,得到了预期的效果,可以临床推广应用。     

大剂量沐舒坦治疗老年慢性阻塞性肺疾病急性发作期的疗效

目的探讨大剂量沐舒坦(盐酸氨溴索)治疗老年慢性阻塞性肺疾病急性发作期的临床疗效及不良反应。方法选取2012年1月至2013年1月于本院进行治疗的60例慢性阻塞性肺疾病急性发作期的患者为研究对象,将其随机分为大剂量组和常规剂量组各30例,两组患者均给予控制感染、祛痰镇咳、解痉平喘及对症处理等常规治疗。大剂量组在常规治疗的基础上加用沐舒坦150 mg+0.9%氯化钠注射液250 mL,2次/d,常规剂量组在常规治疗的基础上加用沐舒坦30 mg+0.9%氯化钠注射液100 mL,2次/d,疗程7～10 d。结果大剂量组显效率76.70%、总有效率93.33%,常规剂量组显效率56.67%、总有效率83.33%,两组比较差异具有统计学意义(P<0.05)。两组患者治疗期间均未出现明显的不良反应,临床用药安全。结论大剂量沐舒坦有显著的排痰作用,联合常规抗炎平喘等治疗慢性支气管炎急性发作疗效确切且用药安全。     

大剂量沐舒坦治疗重型颅脑损伤气管切开后并发肺部感染临床分析

目的 研究大剂量沐舒坦在重度颅脑损伤气管切开后并发肺部感染中的治疗作用.方法 选择重型颅脑损伤气管切开后并发肺部感染患者48例,随机分为对照组和治疗组;治疗组予以静脉滴注沐舒坦(德国勃林格殷格翰公司生产)15 mg/(kg·d),对照组静脉滴注2mg/(kg·d).两组其他用药均相同.比较两组患者痰液黏稠度及胸部X线片.结果 静脉滴注大剂量沐舒坦,可以使肺部痰液易于变得稀薄,痰液更易于咳出和吸出,胸部X线片显示治疗组肺部感染征象控制好于对照组(x2=5.07,P＜0.05).结论 大剂量沐舒坦有助于改善气管切开患者痰液黏调度,促进排痰,控制肺部感染,缩短疗程.     

沐舒坦雾化吸入治疗小儿支气管肺炎的临床分析

目的观察沐舒坦雾化吸入佐治小儿支气管肺炎的临床疗效。方法按照随机原则将80例肺炎患儿分为沐舒坦治疗组40例和对照组40例。对照组给予常规抗感染、吸氧、吸痰等对症支持治疗,治疗组在常规治疗的基础上加用沐舒坦雾化吸入治疗。结果治疗组在改善症状、消除肺部体征及缩短病程等方面优于对照组。结论沐舒坦治疗小儿支气管肺炎,可明显改善呼吸道症状,且不良反应小,值得在临床中应用。     

全麻患者术后肺部感染的原因分析及对策

目的探讨全麻患者术后肺部感染的原因及预防性的应用雾化吸入沐舒坦对预防肺部感染的临床应用价值。方法选择本院进行全麻手术的患者120例,按照随机分组分为观察组和对照组,每组各60例,对照给予常规的术后处理,观察组在对照组治疗的基础上给予患者雾化吸入沐舒坦,观察两组术后肺部感染发生的情况。结果观察组肺部感染发生率低于对照组,经统计学分析比较,差异有统计学意义（P〈0.05）。结论全麻患者手术后预防性雾化吸入沐舒坦可以有效防治肺部感染的发生,值得在临床上大力使用。     

大剂量沐舒坦在高龄食管癌患者术后肺部并发症防治中的应用观察

目的:探讨大剂量沐舒坦在高龄食管癌患者术后肺部并发症防治中的应用价值.方法:所选研究对象为本院收治的择期行手术治疗的高龄食管癌患者,年限为2015年12月～2016年12月,符合标准的有112例.按照随机数字表法,随机分为研究组(大剂量沐舒坦,n=56)与对照组(常规剂量沐舒坦,n=56).对比治疗效果.结果:研究组并发症发生率为10.7％(6/56),对照组并发症发生率为25.0％(14/56),差异有统计学意义(P<0.05);研究组住院时间短于对照组,治疗满意度高于对照组,差异有统计学意义(P<0.05).结论:在高龄食管癌患者手术治疗过程中,辅以大剂量沐舒坦,能减少术后肺部并发症,且能缩短住院时间,提升满意度,值得推广.     

Codeine disposition in human hair after single and multiple doses

Objective: We studied the dose-proportion and time-course relationships for the incorporation of codeine into human hair after the administration of three different doses. Subjects: Male volunteers, with dark hair, were given oral codeine either as a single dose of 60 mg (n = 7) or 120 mg (n = 12), or as multiple doses of 30 mg 3 times daily for 5 days (n = 7) (450 mg total dose). Methods: Blood and urine were collected for various times for up to 72 h after dosing. Scalp hair was collected initially by plucking (up to 4 weeks) and later by cutting for up to 10 weeks. Plasma, urine, proximal 1 cm of hair and distal hair were each analyzed for codeine and its metabolites by positive-ion chemical ionization ion trap gas chromatography/mass spectrometry. Results: Codeine was detected in the proximal 1 cm of hair within 30 min of an oral 120-mg dose. Codeine was not detected in the distal hair segment until 3 weeks after receiving a dose of codeine. Codeine was detected in distal hair segments for at least 10 weeks at 30 pg mg^?1 hair following a single 120 mg codeine dose and at 90 pg mg^?1 hair following 30 mg codeine 3 times a day for 5 days. Morphine or the glucuronides of codeine or morphine were not detected in the hair specimens of these subjects. Conclusion: Codeine is rapidly distributed into the germanitive elements of hair in a dose-proportional manner. A portion of the codeine remains bound as the hair grows and can be detected in distal hair for up to 10 weeks after a single dose.     

Pharmacokinetics and pharmacodynamics of nifedipine infusion in normal volunteers.

Two studies of the pharmacokinetics and pharmacodynamics of intravenous nifedipine infusion were performed: the first, a randomised double-blind crossover study of nifedipine and its vehicle in eight subjects, the second a dose ranging study in nine subjects. Nifedipine pharmacokinetics did not vary with dose or duration of infusion up to 8 h, and are similar to those reported for other nifedipine preparations. Nifedipine increased heart rate and forearm blood flow and decreased blood pressure after bolus injection but not during prolonged infusion. The vehicle decreased blood pressure and increased forearm blood flow after bolus injection but not during prolonged infusion. It did not affect heart rate. The vehicle's haemodynamic activity has not been previously recognised and is of potential importance in the study of this and similar preparations of calcium antagonists.     

The metabolism and excretion of galantamine in rats, dogs, and humans.

Galantamine is a competitive acetylcholine esterase inhibitor with a beneficial therapeutic effect in patients with Alzheimer's disease. The metabolism and excretion of orally administered (3)H-labeled galantamine was investigated in rats and dogs at a dose of 2.5 mg base-Eq/kg body weight and in humans at a dose of 4 mg base-Eq. Both poor and extensive metabolizers of CYP2D6 were included in the human study. Urine, feces, and plasma samples were collected for up to 96 h (rats) or 168 h (dogs and humans) after dosing. The radioactivity of the samples and the concentrations of galantamine and its major metabolites were analyzed. In all species, galantamine and its metabolites were predominantly excreted in the urine (from 60% in male rats to 93% in humans). Excretion of radioactivity was rapid and nearly complete at 96 h after dosing in all species. Major metabolic pathways were glucuronidation, O-demethylation, N-demethylation, N-oxidation, and epimerization. All metabolic pathways observed in humans occurred in at least one animal species. In extensive metabolizers for CYP2D6, urinary metabolites resulting from O-demethylation represented 33.2% of the dose compared with 5.2% in poor metabolizers, which showed correspondingly higher urinary excretion of unchanged galantamine and its N-oxide. The glucuronide of O-desmethyl-galantamine represented up to 19% of the plasma radioactivity in extensive metabolizers but could not be detected in poor metabolizers. Nonvolatile radioactivity and unchanged galantamine plasma kinetics were similar for poor and extensive metabolizers. Genetic polymorphism in the expression of CYP2D6 is not expected to affect the pharmacodynamics of galantamine.     

茴香注射液热原检查方法学研究

目的:验证红茴香注射液热原检查的适用性。方法:参考《中国药典》2010年版一部附录中药注射剂安全性检查法应用指导原则,对红茴香注射液进行热原检查的方法学验证。结果:红茴香注射液原液在剂量为1 mL.kg-1有一定的毒性反应,不适宜进行热原试验;10倍稀释液对热原检查无干扰。结论:可用热原检查法检查红茴香注射液中可能存在的热原,浓度为其10倍稀释液,剂量为1 mL.kg-1。     

Haemodynamic evaluation of two regimens of molsidomine in patients with chronic congestive heart failure

We investigated the extent and duration of the haemodynamic effects of two regimens of molsidomine, i.e. two tablets of a standard regimen consisting of 4 mg given 6 h apart and one tablet of 16 mg in sustained-release form once daily in 13 patients with chronic congestive heart failure using a placebo-controlled, randomized, double-blind and crossover protocol over a period of 12 h. Both regimens significantly affected systolic, mean and diastolic pulmonary arterial pressure (reductions of up to 15%), right atrial pressure (reductions of up to 35%) and total pulmonary resistance (reductions of up to 18%). The lower dose achieved its maximum action after about 1 h and remained effective for 2 h, whereas the higher dose in sustained-release form showed maximal efficacy at 2 h and remained active even at 12 h. In contrast, only minor changes in arterial blood pressure, systemic vascular resistance and cardiac output were observed on both regimens, almost exclusively at 2 h. Heart rate was not affected by either of the regimens tested. Neither regimen led to any untoward adverse effects. Thus, molsidomine is a potent vasodilating agent which, apart from its effects on preload, also acts on pulmonary arterial and right atrial pressures, leaving systemic circulation largely unaffected on the regimens tested. Administered on its own, it is therefore suitable for treatment of congestive heart failure.     

Comparison of potential risks of lactic acidosis induction by biguanides in rats

Lactic acidosis has been considered to be a side effect of some biguanides, after phenformin was withdrawn from the market because of its association with lactic acidosis. The potential of lactic acidosis induced by biguanides at human therapeutic exposure levels, however, has not been examined. Then, we compared the risk of lactic acid at doses providing exposure levels comparable to human therapeutic doses. Metformin and phenformin were orally administered to rats for up to 28 days, and plasma drug concentrations and blood lactic acid levels were examined. Metformin did not elevate lactic acid levels at the dose corresponding to higher systemic drug exposure than human therapeutic level, even for repeated doses. In contrast, phenformin elevated lactic acid levels at the dose corresponding to lower exposure than human therapeutic level, and sustained high levels were observed up to 24 h post-dose; furthermore, these changes were enhanced by repeated doses. Direct comparison at each rat equivalent dose clearly indicated that lactic acid levels of phenformin were higher than those of metformin. These non-clinical findings suggest that metformin dose not increase lactic acid levels like phenformin does, and therefore may not increase the risk for lactic acidosis at human therapeutic exposure level.     

Safety evaluation of a standardized phytochemical composition extracted from Bacopa monnieri in Sprague--Dawley rats.

BacoMind is an enriched phytochemical composition derived from Bacopa monnieri, a common medicinal plant having multiple uses in the traditional system of medicine and particularly used as a memory enhancing agent for centuries. The plant and its extracts have been evaluated for anti-inflammatory, cardio tonic, sedative and neuro-muscular blocking activities. In view of the extensive use of this plant, BacoMind , standardized to bioactive compounds was evaluated in a series of toxicity studies, to confirm the safety of its usage. BacoMind , on single oral administration had a median lethal dose of 2,400 mg/kg in Sprague-Dawley rats. In a 14 day repeated dose oral toxicity study in rats, except for mild lowering in body weight gain in male rats, it was found to be tolerated well up to the dose of 500 mg/kg. A subchronic oral toxicity study for 90 days in rats at the dose levels of 85, 210 and 500 mg/kg did not reveal any evidence of toxicity with respect to clinical signs, neurological examination, food consumption, body weight gain, haematological and blood biochemistry parameters. The absolute and relative organ weight of vital organs did not differ significantly from that of the control. Necropsy and histopathological examination, did not reveal any remarkable and treatment related changes. A no-observed adverse effect level of 500 mg/kg body weight was established in rats.     

Pharmacokinetic profile of dexloxiglumide

Dexloxiglumide is a potent and selective cholecystokinin type 1 (CCK1) receptor antagonist currently under development in a variety of diseases affecting the gastrointestinal tract such as gastro-oesophageal reflux disease, irritable bowel syndrome (IBS), functional dyspepsia, constipation and gastric emptying disorders. In female patients with constipation-predominant IBS, clinical efficacy has been demonstrated following administration of dexloxiglumide 200 mg three times daily. Dexloxiglumide is rapidly and extensively absorbed after single oral administration in humans with an absolute bioavailability of 48%. The incomplete bioavailability is due to both incomplete absorption and hepatic first-pass effect. Following multiple-dose administration of 200 mg three times daily, the accumulation is predictable, indicating time-independent pharmacokinetics. In addition, dexloxiglumide pharmacokinetics are dose-independent after both single and repeated oral three-times-daily doses in the dose range 100-400 mg. Dexloxiglumide absorption window extends from the jejunum to the colon and the drug is a substrate and a weak inhibitor of P-glycoprotein and multidrug resistance protein 1. Plasma protein binding of dexloxiglumide is 94-98% and the drug has a moderate to low volume of distribution in humans. Systemic clearance of dexloxiglumide is moderate and cytochrome P450 (CYP) 3A4/5 and CYP2C9 have been implicated in the metabolism of dexloxiglumide to produce O-demethyl dexloxi-glumide. This metabolite is further oxidised to dexloxiglumide carboxylic acid. These two major metabolites (accounting for up to 50% of dexloxiglumide elimination) have been identified. However, in human plasma the unchanged drug represents the major (up to 91%) component of the metabolic profile. The parent drug is believed to be the major contributor to the efficacy of the compound, since its major metabolites are pharmacologically inactive. In addition, the drug is a single isomer chiral drug (eutomer) that does not undergo chiral inversion into its pharmacologically inactive enantiomer (distomer). After oral administration of (14)C-dexloxiglumide, radioactivity is mainly excreted in bile and in faeces (74% of dose) with much lower excretion in urine (20% of dose). Renal excretion of unchanged dexloxiglumide is low (7% of dose in urine and faeces, 1% of dose in urine) and is dose-independent in the dose range 100-400 mg. As the kidney is a minor contributor to the elimination of dexloxiglumide and/or its metabolites in humans, the pharmacokinetics of the drug should not be affected in patients with renal insufficiency. The pharmacokinetics of dexloxiglumide are also not affected by age, sex and administration with a high-fat breakfast. Mild and moderate liver impairment do not affect the pharmacokinetics of dexloxiglumide but severe liver impairment causes increases in systemic exposure to dexloxiglumide and O-demethyl dexloxiglumide. Thus, the drug should be prescribed with caution in patients with severe hepatic impairment even though no dose adjustment is warranted. The results of different drug interaction studies have indicated that no clinically relevant metabolic and concomitant drug-drug interactions are expected during the clinical use of dexloxiglumide.     

Trials of the bronchodilator activity of the xanthine analogue SDZ MKS 492 in healthy volunteers during a methacholine challenge test

Summary An approximately steady-state reduction of specific airway conductance was induced in healthy human subjects by means of an individualized inhaled methacholine loading dose followed by a maintenance dose regime.Tested against this background bronchoconstriction, the xanthine analogue SDZ MKS 492, when administered as a single oral dose of 40 mg, showed a significant bronchodilator action, which lasted for up to 5.5 h. Bronchodilatation was not seen after administration of 10 or 20 mg doses.SDZ MKS 492 inhaled as a dry powder had a bronchodilator action that was small, most evident with the 12 mg dose and transient. The peak relief of imposed bronchoconstriction was 29% and the apparent half-time of removal of SDZ MKS 492 from its site of action was 5–6 min.Inhaled SDZ 492 had a bitter taste that was not masked by inclusion of menthol and aspartame in the formulation.The bronchodilatation seen in laboratory animals can also be produced by SDZ MKS 492 in man when administered orally or by inhalation. Its magnitude correlates better with the plasma concentration of parent drug than with that of either of the identified metabolites. Dispositional processes in the lung abbreviate its action after administration by inhalation.     

Immunotoxicity assessment for the novel Spleen tyrosine kinase inhibitor R406

Spleen tyrosine kinase (Syk) is a novel pharmaceutical target for treatment of allergic, autoimmune, and neoplastic disorders. Previous studies have indicated that Syk signaling plays critical roles in regulating the lymphohematopoietic system. These observations prompted us to investigate whether inhibition of Syk would promote immunotoxicity. In a series of studies, rats were treated orally with R406, at dose levels up to and including 100 mg/kg/day (or its prodrug R788 at dose levels up to and including 100 mg/kg/day, reduced to 50 mg/kg/day for females as MTD was exceeded), a potent Syk inhibitor, twice daily for 28 days. In addition to standard toxicological assessments, immunophenotyping by flow cytometric analysis, and a study of humoral immune response measuring anti-KLH IgM and IgG levels, were undertaken. Other immunotoxicity studies included three host resistance models in female Balb/c mice to further ascertain effects of R406 on innate and acquired immunity. Following R406 treatment, expected immunomodulating effects (e.g., decreased thymic and spleen weight, hypocellularity of bone marrow, and reduced lymphocyte counts, including T and B cells) were observed in the rat studies. These changes essentially resolved during a 14-day treatment-free recovery period. A KLH challenge in rats demonstrated no adverse effects on IgG or IgM response. R788/406, administered orally at dose levels up to and including 80 mg/kg/day for 28 days, did not affect bacterial or viral clearance in the Listeria, Streptococcal, or Influenza host resistance mouse models, respectively. This correlated with previous in vitro macrophage and neutrophil function assays (assessing migration, phagocytosis, oxidative burst and microbicidal activity), which revealed that R406 did not adversely affect macrophage or neutrophil function in innate immune responses. Collectively, these results demonstrate that R406 has minimal functional immunotoxicity notwithstanding its lymphocytopenic effect, suggesting that inhibition of Syk might not lead to unacceptable mechanism-based adverse effects.