丁丙诺啡舌下片合并东莨菪碱、异丙嗪药物依赖者脑白质完整性的研究

目的:观察在中国南方新近出现的盐酸丁丙诺啡舌下片合并东莨菪碱、异丙嗪药物依赖者(简称BSP依赖者)脑白质完整性的变化,并比较其与海洛因依赖者脑结构损害的异同.方法:采用弥散张量成像方法对16例BSP依赖者、20例海洛因依赖者停药3 d各向异性分数(fractional anisotropy,FA)进行组间对照研究,并设...     

An evaluation of the effects of high-dose fexofenadine on the central nervous system: a double-blind, placebo-controlled study in healthy volunteers.

BACKGROUND: As regards central nervous system (CNS) effects there are three types of antihistamines. Those that cross the blood-brain barrier and cause widespread impairment of cognitive and psychomotor function; those that cross into the brain and, although without much impairment at low clinical doses, have a dose-related relationship to impairment; and those that do not cross into the brain and therefore possess no intrinsic potential for impairing CNS function. OBJECITVE: To investigate the acute effects of fexofenadine (360 mg) on various aspects of cognitive and psychomotor function in comparison to placebo and promethazine (positive internal control), an antihistamine known to produce psychomotor and cognitive impairment. METHODS: Fifteen healthy volunteers received fexofenadine 360 mg, promethazine 30 mg and placebo in a 3-way cross-over, double-blind study. For each treatment condition, subjects were required to perform a series of tests of cognitive function and psychomotor performance at baseline and 1, 3, 5 and 7 h post-dose. The test battery consisted of critical flicker fusion (CFF), choice reaction time (CRT), compensatory tracking task (CTT) and a subjective assessment of sedation (LARS). RESULTS: Fexofenadine was not distinguishable from placebo in any of the objective and subjective tests for up to seven hours following drug administration. However, all measures were significantly impaired following the administration of promethazine, which confirms the sensitivity of the test battery for sedation. The effects of fexofenadine and placebo were not significantly different from one another, whereas promethazine caused an overall reduction in CFF thresholds when compared to placebo (P < 0.05). There was an overall significant increase (impairment) in recognition, motor and total reaction time (P < 0.05), and both the tracking accuracy and reaction time aspects of CTT were significantly impaired (P < 0.05) following the administration of promethazine. In contrast, the effects of fexofenadine could not be distinguished from the placebo condition. Subjective ratings of sedation were significantly higher with promethazine when compared to placebo (P < 0.05) and fexofenadine (P< 0.05). CONCLUSIONS: Fexofenadine at a dose of 360mg is demonstrably free from disruptive effects on aspects of psychomotor and cognitive function in a study where the psychometric assessments have been shown to be sensitive to impairment, as evidenced by the effects of the verum control promethazine 30 mg. The identification of an antihistamine (fexofenadine) devoid of central effects even at supraclinical doses separates it from currently available first and second generation drugs with no objective evidence of CNS side-effects on cognition and psychomotor function, and highlights the need for the introduction of a third generation of non-sedative antihistamines.     

伤风止咳糖浆中愈创木酚磺酸钾的分光光度测定法

采用三阶导数分光光度法,可以消除盐酸异丙嗪和苯甲酸钠的干扰,测定伤风止咳糖浆中愈创木酚磺酸钾的含量,平均回收率100.18%,变异系数0.56%。     

生物检材中复方芬太尼的气相色谱和气相色谱/质谱检测

目的:建立生物检材中复方芬太尼的气相色谱(GC)和气相色谱/质谱检测方法(GC/MS法)。方法:检材经10%氢氧化钠调pH=10,乙醚萃取,气/质联用法定性,气相色谱内标法定量检测生物检材中复方芬太尼。结果:GC/MS法分析芬太尼的选择离子m/z为245,146;异丙嗪的选择离子m/z为284,72。GC检测的回归方程、线性检测范围、相关系数、回收率、最低检出浓度分别为:心血中芬太尼为Y=23.376X+0.516 8(μg/mL),(0.1~220)μg/mL,0.985,(98.5±3.5)%,0.1μg/mL,异丙嗪为Y=16.537X+0.158 4(μg/mL),(0.12~200)μg/mL,0.974,(97.50±2.0)%,0.12μg/mL;肝组织中芬太尼为Y=82.236X+0.413 4(μg/mL),(0.1~220)μg/g,0.975,(95.6±0.75)%,0.1μg/g,异丙嗪为Y=40.437X+0.134 2(μg/mL),(0.12~200)μg/g,0.964,(94.8±0.15)%,0.12μg/g。染毒家兔心血及心、肝、脾、肺、肾和脑中芬太尼的含量依次为:(24.39±6.43)μg/mL及(84.96±1.03),(73.82±1.73),(55.74±2.07),(42.64±1.38),(35.94±2.87),(10.15±7.05)μg/g,异丙嗪的含量依次为:(146.69±2.43)μg/mL及(204.96±13.03),(213.32±1.73),(115.74±3.07),(95.64±5.38),(195.34±2.87),(170.15±1.05)μg/g。结论:生物检材中GC/MS法选择性好,定性准确,GC检测简便,快速,灵敏,定量结果准确,可用于芬太尼麻醉意外中毒的临床快速检验诊断和芬太尼滥用中毒死亡案件的法医学鉴定。     

13厂家盐酸西替利嗪片溶出度考察

目的比较国内不同厂家生产盐酸西替利嗪片溶出度的差异。方法采用转蓝法、紫外-可见分光光度法测定盐酸西替利嗪的含量,计算累积溶出量。结果其中11家企业的产品符合《中国药典》相关规定,2家生产企业2批次产品不符合《中国药典》相关规定。各厂家产品溶出行为差异较大。结论不同厂家生产的盐酸西替利嗪片的溶出行为存在较大差异,临床用药时应加以注意。     

差示分光光度法测定盐酸异丙嗪糖浆中盐酸异丙嗪含量

目的建立测定盐酸异丙嗪糖浆中盐酸异丙嗪含量的差示分光光度法。方法采用差示分光光度法,检测波长为336.5 nm。结果盐酸异丙嗪检测质量浓度在10.00～50.02μg/mL范围内与差示吸光度值线性关系良好(r=0.999 9);平均回收率为99.82%,RSD=0.23%(n=6)。结论所用方法操作简便、准确可靠、重复性好、专属性强,可用于该制剂的质量控制。     

DNA修饰电极上盐酸异丙嗪电化学行为及其电化学动力学性质

目的:研究盐酸异丙嗪(promethazine hydrochloride)在DNA修饰碳糊电极(DNA/CPE)上的电化学行为及电化学动力学性质。方法:用循环伏安法(CV)、线性扫描伏安法(LSV)、计时库仑法(CC)和计时电流法(CA)等多种电化学方法进行研究。结果:在pH=6.8的C-L缓冲溶液中,1.0×10-4mol.L-1的盐酸异丙嗪在DNA/CPE上氧化峰电位为0.633 V,比在碳糊电极(carbon paste electrode,CPE)上的峰电位正移了30 mV,峰电流显著降低。测得盐酸异丙嗪在DNA/CPE上电极反应动力学参数:电荷转移系数α=0.80,扩散系数D=8.936×10-6cm2.s-1,电极反应速率常数kf=3.828×10-2cm2.s-1,而在CPE上α=0.86,扩散系数D=1.099×10-5cm2.s-1。结论:盐酸异丙嗪与DNA二者以嵌插作用结合,形成了一种非电活性物质。     

Applications in drug analysis of carbon paste electrodes modified by fatty acids

The oxidation of promethazine as a model compound has been studied by adsorptive stripping voltammetry at carbon paste electrodes (CPE). A modification of the carbon paste matrix with fatty acids allows greater preconcentration of the molecule at the electrode surface. Several fatty acids of different chain length have been tested. The modification of the CPE with lauric acid has been successfully applied in the quantiative analysis of promethazine in standard serum samples. The influence of several parameters affecting the accumulation step has been investigated such as: pH, ionic strength, interfering ions, paste composition. The detection limit in phosphate buffer at pH 9.0 (t_acc = 5 min) has been found to be 1 × 10⁻¹⁰ M.     

Study of the prophylactic effect of droperidol, alizapride, propofol and promethazine on spinal morphine-induced pruritus

Background. We have compared the use of alizapride, propofol,droperidol and promethazine for the prevention of spinal morphine-inducedpruritus. Methods. Three hundred ASA I or II women undergoing Caesareansection under spinal anaesthesia, in which morphine 0.2 mg wasadded to a local anaesthetic, were assigned randomly to receivei.v., in the operating room, just after delivery of the baby,alizapride 100 mg, propofol 20 mg, droperidol 1.25 mg, promethazine50 mg or saline 2 ml (control group). In the postoperative period,the women were assessed for pruritus (absent, mild, moderateor severe) or other untoward symptoms by blinded observers.We used 95% confidence limits (95% CI) for the cumulative incidenceof moderate and severe pruritus to compare the groups, and theNNT and 95% CI to compare droperidol, propofol and alizaprideas for their effectiveness in preventing pruritus. For otheruntoward effects, the