右美沙芬治疗甲氨蝶呤中枢毒性反应26例文献汇总分析

目的： 探讨甲氨蝶呤化疗相关中枢神经系统毒性的临床特征、机制以及治疗方法。方法： 进行国内外文献复习,汇总分析右美沙芬治疗甲氨蝶呤化疗相关中枢神经毒性的病例,总结作用机制和治疗效果。结果： 文献回顾共26例患者静脉输注或鞘注甲氨蝶呤后2~14 d出现中枢毒性反应,表现为肢体运动或（和）感觉障碍、言语障碍、意识障碍、震颤等,给予口服右美沙芬治疗后24例症状完全缓解,2例观察期有后遗症。平均起效时间10.1 h,平均缓解时间10.8 d。结论： 右美沙芬是甲氨蝶呤中枢神经毒性潜在的特异性治疗药物,症状出现后及早给药（<24 h）可缩短起效时间和缓解时间。     

GDP/ML化疗方案相关成人严重神经系统不良反应3例

3例应用GDP/ML联合化疗方案(甲氨蝶呤、吉西他滨、顺铂、培门冬酶、地塞米松)治疗的鼻型NK/T细胞淋巴瘤患者,输注大剂量甲氨蝶呤后48 h内出现双下肢感觉及运动丧失,伴言语障碍、意识障碍等,经积极治疗无明显好转。提示以GDP/ML方案治疗鼻型NK/T细胞淋巴瘤有发生严重中枢不良反应的风险。结合国内外文献回顾发现,口服右美沙芬具有潜在的治疗意义。     

右美沙芬缓释混悬液的生物等效性研究

在 18名男性健康受试者中研究国产右美沙芬缓释混悬液的药物动力学特性及生物等效性。采用双周期交叉设计 ,反相高效液相色谱 -荧光检测法测定血浆中右美沙芬活性代谢物去甲右美沙芬的浓度。单剂量口服 6 0 m g右美沙芬缓释混悬液与进口对照品的 cmax分别为 4 36 .8± 116 .7和 4 0 9.5± 113.7ng/m l;Tmax为 3.3± 1.0和 3.4±0 .8h;T1 /2 为 7.5± 2 .7和 7.5± 3.1h;AUC0→ tn为 3435± 6 6 4 .2和 32 6 9± 6 2 6 .0 ng· ml- 1 · h。多剂量服药达稳态后两制剂的波动度分别为 (12 1.9± 37.1% )和 (133.2± 4 0 .6 ) %。主要药动学参数经统计学检验表明 :国产右美沙芬缓释混悬液与进口同类产品具生物等效性 ,相对生物利用度为 (10 5 .9± 13.8) %。     

柱切换HPLC法测定血浆中氢溴酸右美沙芬的代谢物去甲右美沙芬

应用柱切换HPLC法建立了氢溴酸右美沙芬的主要代谢产物去甲右美沙芬的血浆浓度测定方法。去甲右美沙芬的葡萄糖醛酸结合物,经β-葡萄糖醛酸苷酶水解后,即可取血浆直接进行HPLC分析。预处理柱为30 mm×5 mm ID,内装μBondapak C₁₈,37～50μm;分析柱为150 mm×5 mmID,内装YWG-C₁₈,10μm。预处理流动相为0.2%的乙酸溶液,流速3 ml/min;分析流动相为乙腈—水—乙酸—三乙胺—二氯甲烷(17:82:1:0.05:0.025)的混合溶液,流速1 ml/min荧光检测波长分别为λex=290 nm和λem=315 nm。血浆浓度测定的线性范围为20～640 ng/ml,血浆中最低检测浓度为4ng/ml,方法的平均回收率为103.8%,日内及日间变异均小于10%。     

右美沙芬的滥用及合理使用

右美沙芬(dextromethorphan)又名右甲吗喃、美沙芬、普西兰,由瑞士罗氏(Roche)公司开发,1956年被美国食品药品监督管理局(FDA)列为非处方药,且被美国FDA誉为"现代最安全"的中枢镇咳药;1961年在世界麻醉药会议上被定为非麻醉药;1989年,世界卫生组织认为"右美沙芬是取代可待因的一种镇咳药";美国药物索引(American Drug Index)收集右美沙芬制剂单方9个、复方67个,均为口服剂型,如片剂、胶囊、糖浆和溶液等.它的氢溴酸盐常用于药品中[1].     

氢溴酸右美沙芬口服液在正常人体内的生物利用度

氢溴酸右美沙芬剂量小,体内代谢迅速而广泛,母体药物浓度测定困难。本文通过测定氢溴酸右美沙芬的主要活性代谢物——去甲右美沙芬的血药浓度,进而对氢溴酸右美沙芬口服液在正常人体内的生物利用度进行研究。结果表明,8例正常人口服氢溴酸右美沙芬30mg 后,在体内可迅速转化为去甲右美沙芬,约在2h 达高峰浓度,T_(1/2)在1.7～4.7h。口服液的Tmax 较片剂明显提前,统计学t 检验有显著性差异(P<0.05);但Cmax 和AUC 在两种剂型间基本一致。     

右美沙芬的合理使用

目的重新认识右关沙芬的安全性。方法罗列井分析近年采右美沙芬在使用中出现的不良反应。结果滥用右美沙芬会导致成瘾性和其他不良反应。结论必须重视右美沙芬的安全合理使用.     

HPLC法测定人尿中右美沙芬及去甲右美沙芬的含量及CYP2D6表型区分研究

目的:建立以高效液相色谱法测定人尿中右美沙芬及去甲右美沙芬含量的方法,并行CYP2D6表型区分。方法:尿样经酶水解,酸、碱提取纯化,直接进样。其中色谱柱为Waters Nova-Pak Phenyl,流动相为乙腈-水(60∶40),流速为1.0mL.min-1,激发波长为280nm,发射波长为310nm,柱温为25℃。结果:右美沙芬、去甲右美沙芬尿药浓度分别在0.065~4.148(r=0.9985)、0.353~22.592(r=0.9997)μg.mL-1范围内线性关系良好,最低检测限分别为0.016、0.018μg.mL-1,平均加样回收率各为90.5%、93.5%,日内RSD各≤3.26%、≤3.47%,日间RSD各≤3.65%、≤4.05%。8位受试者均为CYP2D6快代谢型。结论:本方法简便可靠,适用于人尿中右美沙芬及去甲右美沙芬含量测定和CYP2D6多态性的表型研究。     

人尿中右美沙芬及代谢物的高效液相色谱测定法

用反相高效液相色谱法测定人尿中右美沙芬(DM)及其代谢物去甲右美沙芬。尿样经酸、碱提取纯化,直接进样HPLC系统。样品经苯基柱分离后在荧光(激发波长280nm,发射波长310nm)下检测,以乙腈—含10mmol·L^-1 KH₂PO₄,10mmol·L^-1庚磺酸盐水溶液(35∶65,pH4.0)为流动相,外标法定量。DM的最低检测浓度为0.023mg·L^-1。DM和DX的日内和日间相对标准差均小于5%。平均回收率为104.90%。本法为临床筛选异喹胍羟化酶活性与合理用药提供了一种简便、安全的方法。     

氢溴酸右美沙芬咀嚼片生物利用度研究

目的 :研究氢溴酸右美沙芬咀嚼片在健康人体内的药动学和生物利用度。方法 :采用高效液相色谱法测定 1 0例健康志愿者 ,单剂量一次口服 60mg国产氢溴酸右美沙芬片与氢溴酸右美沙芬咀嚼片后右美沙芬的血药浓度变化情况 ,计算二者的药动学参数及相对生物利用度 ,以AUC0 - 12 ,Tmax,Cmax为指标 ,配对t检验法分析两药的生物等效性。结果 :两药的药时曲线可用单室模型拟合 ,其药动学参数分别为t1/2 :2 75± 0 87h和2 92± 1 0 3h ;Tmax:1 81± 0 59h和 1 75± 0 65h ;Cmax:3 1 0 9± 1 1 0 1ng·ml- 1和 3 3 0 9± 1 3 4 8ng·ml- 1;AUC0 - 12 :1 69 1 2± 82 94和 1 66 95± 78 2 3ng·h·ml- 1,其相对生物利用度 (F % )为 1 0 4 0 2± 1 0 3 7% ;结论 :对照药和试验药两种制剂中右美沙芬的t1/2 、Tmax和Cmax经配对t检验无显著差异 (P >0 0 5) ;AUC0 - 12 值经方差分析 ,双单测t检验、 ( 1 -2α) 90 %置信限等统计处理合格 ,说明两种制剂为生物等效制剂     

毛细管气相色谱法测定人尿中右美沙芬及其代谢物

目的：为研究细胞色素Ｐ４５０同工酶ＣＹＰ２Ｄ６在人群中的代谢多态性。本文建立了人尿中右美沙芬（ＤＭ）及其Ｏ－去甲基代谢物３－羟基－Ｎ－甲基－吗喃（ＤＴ）的气相色谱分析方法。方法：尿样经提取后,以ＨＰ－１毛细管柱作为分离柱,ＦＩＤ为检测器,正二十烷为内标进行气相色谱分析。结果：在此实验条件下,右美沙芬、内标物和代谢物的保留时间分别为８．５、９．９和１１．２ｍｉｎ;尿样中ＤＭ在０．１０－２．０μｇ／ｍ     

重型颅脑损伤患者神经功能康复的护理干预分析

目的探讨不同的干预措施对于重型颅脑损伤患者神经功能康复的效果。方法将我院2012年1月1日到2012年12月31日收治的110例颅脑损伤患者作为研究对象,随机将患者分为对照组和研究组,每组55例,对照组患者采用常规护理,研究组患者在人院当天即进行早期的干预措施,比较两组患者在治疗上的效果。结果研究组患者经过皮肤刺激、穴位刺激、被动活动关节、肢体按摩、膀胱功能训练等护理措施后,功能恢复较对照组患者好,两组患者出院时Barther指数评分疗效、Fugl-Meyer评定疗效间差异具有统计学意义,P〈0．05。结论早期护理干预有利于患者神经功能的康复,能够有效降低患者的伤残率,显著改善患者的生活质量。     

高压氧在重症颅脑损伤的应用

目的探讨提高重症颅脑损伤治疗的成功率,加快重症颅脑损伤患者的恢复,减少并发症,提高预后生活质量和降低死亡率。方法将我院自1990年收治的部分重症颅脑损伤患者,80例患者随机分为实验组和对照组,每组40例,实验组在常规综合治疗的基础上加用高压氧治疗,对照组只给予常规综合治疗。对两组患者进行跟踪观察,分别于实施高压氧治疗一个疗程后作格拉斯哥昏迷评分(GCS)和评价。结果实验组在加用高压氧治疗一个疗程后,格拉斯哥昏迷评分及病死率与对照组之间差异有统计学意义(P<0.05)。结论高压氧可提高重症颅脑损伤治疗效果,减低伤残率及死亡率,疗效满意,毒副作用小。     

Comparing effects of methylphenidate, sertraline and placebo on neuropsychiatric sequelae in patients with traumatic brain injury

BACKGROUND: This study aimed to investigate the effects of methylphenidate and sertraline compared with placebo on various neuropsychiatric sequelae associated with traumatic brain injury (TBI). METHODS: This was a 4 week, double-blind, parallel-group trial. Thirty patients with mild to moderate degrees of TBI were randomly allocated to one of three treatment groups (n = 10 in each group) with matching age, gender and education, i.e. methylphenidate (starting at 5 mg/day and increasing to 20 mg/day in a week), sertraline (starting at 25 mg/day and increasing to 100 mg/day in a week) or placebo. At the baseline and at the 4 week endpoint, the following assessments were administered: subjective (Beck Depression Inventory) and objective (Hamilton Depression Rating Scale) measures of depression; Rivermead Postconcussion Symptoms Questionnaire for postconcussional symptoms; SmithKline Beecham Quality of Life Scale for quality of life; seven performance tests (Critical Flicker Fusion, Choice Reaction Time, Continuous Tracking, Mental Arithmetic, Short-Term memory, Digit Symbol Substitution and Mini-Mental State Examination); subjective measures of sleep (Leeds Sleep Evaluation Questionnaire) and daytime sleepiness (Epworth Sleepiness Scale). All adverse events during the study period were recorded and their relationships to the drugs were assessed. RESULTS: Neuropsychiatric sequelae seemed to take a natural recovery course in patients with traumatic brain injury. Methylphenidate had significant effects on depressive symptoms compared with the placebo, without hindering the natural recovery process of cognitive function. Although sertraline also had significant effects on depressive symptoms compared with the placebo, it did not improve many tests on cognitive performances. Daytime sleepiness was reduced by methylphenidate, while it was not by sertraline. CONCLUSIONS: Methylphenidate and sertraline had similar effects on depressive symptoms. However, methylphenidate seemed to be more beneficial in improving cognitive function and maintaining daytime alertness. Methylphenidate also offered a better tolerability than sertraline.     

重型颅脑损伤术中脑膨出原因分析及临床对策

目的探讨重型颅脑损伤手术中脑膨出形成的原因及临床对策。方法回顾性分析本院收治的98例重型颅脑损伤患者的病例资料,分析其术中出现急性脑膨出的原因,总结临床工作中具体实施的临床对策及有效方法。结果患者予急诊开颅手术治疗,术中针对脑膨出积极治疗。术后恢复良好19例,中残22例,重残12例,植物生存11例,死亡34例。结论急性弥漫性脑肿胀及迟发性颅内血肿是导致术中出现脑膨出的主要原因,根据患者的情况应该早做分析,针对不同原因及时采取综合治疗处理措施,可以提高救治脑膨出成功率。     

Effects of chronic dextromethorphan administration on the cellular immune responses in mice

We examined the chronic effect of dextromethorphan (DM) on the cellular immune responses in mice. T cell stimulator, phytohemagglutinin did not show significant effect on lymphocyte proliferation. Costimulator of T and B cell, pokeweed mitogen, and B cell stimulator, lipopolysaccharide exhibited DM-induced decreased lymphocyte proliferation. Significantly suppressed natural killer (NK) cell cytotoxicity was evidenced following 6 months DM exposure. These results suggest that chronic DM administration perturb B cell functioning and NK cell cytotoxicity. In addition, prenatal DM exposure did not potentiate the immunomodulation in postnatal effect induced by chronic DM.     

Determination of dextromethorphan metabolizer phenotype in healthy volunteers

Summary The dextromethorphan metabolizer phenotype in 450 healthy volunteers (299 men, 151 women) was determined after oral administration of a 15 mg dose. In 8 h-postdose urine samples the ratio of dextrorphan (DOP) to dextromethorphan (DMP) was measured by HPLC.Urinary excretion of DMP and DOP within 8 h after the dose varied greatly between individuals, ranging from 0–11% and 0.04–100% of dose, respectively. In 143 test subjects the fraction of the dose of DMP in urine was below the detection limit. In the remaining 307 volunteers the metabolic ratio (MR) of DOP to DMP varied from 0.07 to 2906. In 404 test subjects the MR was >10 and they were classified as extensive metabolizers (90% of the entire group). Of the entire group 5% had MRs of 1–10 and <1, respectively. Depending on the limit for classification of poor metabolizers, their frequency was 5–10% in the Caucasian population studied.The present data are in agreement with previous findings that the oxidative metabolic polymorphisms of debrisoquin and DMP co-segregate; the frequency of the PM phenotype of dextromethorphan in Caucasian populations varies between 5 and 10%.     

氢溴酸右美沙芬片健康人体生物等效性

目的 :研究氢溴酸右美沙芬片在健康人体的药动学及相对生物利用度。方法 :8名健康受试者单剂量随机交叉口服氢溴酸右美沙芬片参比制剂和被试制剂 6 0mg ,采用HPLC法测定用药后不同时间的血药浓度。结果 :2种制剂的体内过程均符合一房室开放模型 ,参比制剂和被试制剂的tmax分别为 (2 72± 0 2 1)h和 (2 74± 0 19)h ,cmax分别为 (5 5 1± 0 4 4) μg·L-1和(5 5 8± 0 2 7) μg·L-1,AUC分别为 (4 5 3± 2 9) μg·h·L-1和 (4 5 7± 3 0 ) μg·h·L-1,被试制剂的相对生物利用度为 (10 1±5 9) %。结论 :2种制剂具有生物等效性。     

Brain-derived neurotrophic factor delivered to the brain using poly (lactide-co-glycolide) nanoparticles improves neurological and cognitive outcome in mice with traumatic brain injury

Currently, traumatic brain injury (TBI) is the leading cause of death or disabilities in young individuals worldwide. The multi-complexity of its pathogenesis as well as impermeability of the blood–brain barrier (BBB) makes the drug choice and delivery very challenging. The brain-derived neurotrophic factor (BDNF) regulates neuronal plasticity, neuronal cell growth, proliferation, cell survival and long-term memory. However, its short half-life and low BBB permeability are the main hurdles to be an effective therapeutic for TBI. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles coated by surfactant can enable the delivery of a variety of molecules across the BBB by receptor-mediated transcytosis. This study examines the ability of PLGA nanoparticles coated with poloxamer 188 (PX) to deliver BDNF into the brain and neuroprotective effects of BNDF in mice with TBI. C57bl/6 mice were subjected to weight-drop closed head injuries under anesthesia. Using enzyme-linked immunosorbent assay, we demonstrated that the intravenous (IV) injection of nanoparticle-bound BDNF coated by PX (NP-BDNF-PX) significantly increased BDNF levels in the brain of sham-operated mice (p?<?0.001) and in both ipsi- (p?<?0.001) and contralateral (p?<?0.001) parts of brain in TBI mice compared to controls. This study also showed using the passive avoidance (PA) test, that IV injection of NP-BDNF-PX 3?h post-injury prolonged the latent time in mice with TBI thereby reversing cognitive deficits caused by brain trauma. Finally, neurological severity score test demonstrated that our compound efficiently reduced the scores at day 7 after the injury indicating the improvement of neurological deficit in animals with TBI. This study shows that PLGA nanoparticles coated with PX effectively delivered BDNF into the brain, and improved neurological and cognitive deficits in TBI mice, thereby providing a neuroprotective effect.