复方愈麻美芬缓释片在Beagle犬体内的药物动力学研究

目的对Beagle犬服用复方愈麻美芬缓释片和国外对照缓释片的药动学特性和生物利用度进行比较。方法HPLC法测定 6只Beagle犬服药后的血药浓度 ,计算出有关药物动力学参数 ,经统计学分析并将两者的计算参数进行比较。结果 6只Beagle犬服用复方愈麻美芬缓释片的血药浓度与服用国外对照缓释片基本一致。复方愈麻美芬缓释片中愈创木芬甘油醚的tpeak 为(3 0 0 0± 0 14 4 )h ,ρmax为 (13 79± 0 5 70 )mg·L-1,t1/ 2 为 (2 35 3± 0 2 5 5 )h ,AUC为 (139 1±9 0 83)mg·L-1·h ;氧去甲右美沙芬的tpeak为 (4 4 2 9± 0 0 88)h ,ρmax为 (0 30 1± 0 0 4 0 )mg·L-1,t1/ 2 为 (6 4 4 5± 0 5 5 1)h ,AUC为 (4 35 4± 0 4 79)mg·L-1·h ;盐酸伪麻黄碱的tpeak为 (2 6 10±0 14 6 )h ,ρmax 为 (1 174± 0 2 0 6 )mg·L-1,t1/ 2 为 (2 84 4± 0 82 5 )h ,AUC为 (8 2 6 6±2 0 30 )mg·L-1·h。与国外对照缓释片相比 ,复方愈麻美芬缓释片的生物利用度为 :愈创木芬甘油醚为 119 8% ;氧去甲右美沙芬为 10 2 4 % ;盐酸伪麻黄碱为 115 6 % ;两制剂tmax、ρmax和AUC间无显著的统计学差异。结论经双单侧t检验分析 ,服用复方愈麻美芬缓释片后其生物利用度与服用国外对照缓释片等效     

愈美分散片的HPLC测定

建立了HPLC法测定愈美分散片中愈创木酚甘油醚和氢溴酸右美沙芬的含量.采用ODS柱,流动相为乙腈-甲醇-0.01%三乙胺溶液(18:15:67,pH3.5),流速1.0ml/min,检测波长276nm.愈创木酚甘油醚和氢溴酸右美沙芬的线性范围分别为6～72μg/ml和4.2～51μg/ml,平均回收率分别为99.0%和102.6%,RSD分别为1.2%和1.5%.     

Stand-up Conic

Abstract

Adverse drug reactions lead to a significant number of hospital admissions each year and thus contribute to the overall financial burden of health care. Some of these drug reactions are allergic responses. As the overall predictability of allergic responses to drugs remains low, efforts to improve our understanding of the processes underlying these responses continue as we strive toward the ultimate goal of primary prevention. Allergic reactions range from mild pruritic to severe systemic anaphylactic responses. We report a case of a young healthy man who developed an anaphylactic reaction to an over-the-counter expectorant. A skin test showed that the patient had an immunoglobulin E-mediated allergic response to guaifenesin, one of the components of commonly available cough medications. Our review of published literature showed that this is the first report of a severe allergic response to guaifenesin.     

愈酚溴新口服溶液剂的药物动力学和生物等效性研究

在20名男性健康受试者中进行愈酚溴新口服溶液剂人体生物等效性研究,以市售愈创甘油醚片和盐酸溴己新片为参比制剂,剂量为愈创甘油醚400mg、盐酸溴己新16mg。采用LC-MS/MS法同时测定血浆中愈创甘油醚、溴己新和溴己新活性代谢物氨溴索的浓度。研究结果表明:以愈创甘油醚为研究对象,愈酚溴新口服溶液剂的生物利用度高于愈创甘油醚片,平均相对生物利用度为(136.32±29.62)%;以溴己新为研究对象,愈酚溴新口服溶液剂与盐酸溴己新片生物等效,平均相对生物利用度为(106.72±32.19)%。     

愈美颗粒治疗小儿急性呼吸道感染疗效观察

目的评估愈美颗粒对小儿急性呼吸道感染的止咳、化痰、祛痰等临床疗效。方法采用随机对照方法 ,将120例急性呼吸道感染患儿随机分为治疗组和对照组各60例,比较愈美颗粒、复方甘草口服溶液两种药物的总有效率。结果愈美颗粒组至疗程第5d临床症状总有效率（咳嗽88.3%,痰量及痰粘稠度78.3%）均明显优于对照组（P〈0.01）,且药物接受程度高（P〈0.05）。结论愈美颗粒是一种适用于〉2岁小儿急性呼吸道感染的安全有效的止咳化痰药。     

Pharmacokinetics of guaifenesin,pseudoephedrine and hydrocodone in a combination oral liquid formulation,administered as single and multiple doses in healthy Chinese volunteers,and comparison with data for individual compounds formulated as Antuss®

1. A new oral liquid formulation combining guaifenesin, pseudoephedrine and hydrocodone is effective in improving the symptoms of common cold. The pharmacokinetic properties of the individual components were evaluated in a randomized, open-label, four-period study in 12 healthy Chinese volunteers following single and multiple doses. The data were compared with data for the individual ingredients in Antuss®.

2. In the single-dose period, exposure levels (AUC and C_max) for guaifenesin, pseudoephedrine and hydrocodone increased directly as the dose of the oral liquid formulation increased from 5 to 15?mL. Only minor amounts of guaifenesin and hydrocodone were excreted in urine (～0.10% and 4.66%, respectively). Pseudoephedrine was mainly excreted unchanged, with 44.95% of the dose excreted in urine within 24?h. After multiple dosing, there was no obvious accumulation of any drug, as assessed by AUC. When considering C_max, there was a trend toward accumulation of hydrocodone and pseudoephedrine. The pharmacokinetic profiles of guaifenesin and pseudoephedrine in the oral liquid formulation were similar to those in the branded preparation, Antuss®.

3. The newly developed oral liquid formulation combining guaifenesin, pseudoephedrine and hydrocodone was safe and well tolerated and might provide a reliable alternative to the branded formulation for patients with common colds.     

复方愈麻美芬缓释片在健康志愿者体内药动学研究

目的研究复方愈麻美芬缓释片单剂量和多剂量给药在健康志愿者体内的药动学规律。方法采用自身对照的双周期交叉试验设计,12名健康受试者单次和多次口服受试制剂复方愈麻美芬缓释片或相应的参比制剂,不同时间点收集血样,采用LC/MS/MS法测定血浆中愈创甘油醚、伪麻黄碱、右美沙芬和O-去甲右美沙芬的浓度。药动学参数采用DAS软件处理获得。结果单剂量口服受试制剂后,愈创甘油醚、伪麻黄碱、右美沙芬、O-去甲右美沙芬的主要参数为tmax:1.09±0.42、3.68±1.62、5.05±2.29、3.82±1.25 h;t1/2:3.32±3.54、6.20±0.97、12.2±3.1、7.60±0.97 h;Cmax:499±159、96.1±12.9、1.82±1.18、142±34 ng/m L;AUC0-t:2 363±529、1 359±284、31.4±23.6、1 504±242 ng·h/m L;AUC0-∞:2 554±639、1 395±303、38.4±28.4、1 563±248 ng·h/m L。多剂量口服愈创甘油醚、伪麻黄碱、右美沙芬、O-去甲右美沙芬的主要参数为Cmax:709±298、169±27、9.64±6.36、314±96 ng/m L;Cmin:48.9±25.4、50.8±13.9、5.45±5.53、110±45 ng/m L;tmax:8.27±5.71、7.64±4.99、8.27±6.57、7.55±5.99 h;AUC0-t:5 277±2 212、2 741±508、199±198、4 964±1 387 ng·h/m L;AUC0-∞:5 718±2 176、2 750±511、220±226、5 196±1 506 ng·h/m L。结论复方愈麻美芬缓释片各成分药动学具有明显的缓释特征。     

愈酚甲麻那敏分散片的人体药动学研究

目的建立测定人血浆中愈创木酚甘油醚的高效液相法,以研究健康志愿者口服愈酚甲麻那敏分散片后愈创木酚甘油醚的药动学过程。方法色谱条件：Agilent Eclipse XDB—C18为色谱柱,以乙腈-磷酸二氢铵（体积比20：80,浓磷酸调至pH值3．0）为流动相,氧去甲右美沙芬为内标,紫外检测波长为230nm。结果愈创木酚甘油醚质量浓度在25～2000ng·mL^-1范围内线性关系良好（r=0．9977）,定量下限为25ng·mL^-1。20名受试者单剂量口服愈酚甲麻那敏分散片后的主要动力学参数Cmax为（474±142）ng·mL^-1,tmax为（0．275±0．123）h,t1/2为（0．83±0．55）h,AUC0→4为（451±165）ng·h·mL^-1,AUC0→∞为（505±159）ng·h·mL^-1。结论本文所建立的方法简便、准确、可靠,可满足愈创木酚甘油醚临床药动学研究的需要。     

愈酚伪麻待因口服溶液中有关物质检查方法的研究

目的 建立愈酚伪麻待因口服溶液中有关物质的检查方法.方法 采用反相高效液相色谱法:DiamonsilTM-C18柱,乙腈-0.01 mol·L-1的磷酸二氢钾(内含0.002 mol·L-1的庚烷磺酸钠,用磷酸调pH=3.0)(体积比30:70)为流动相,流速为1 mL·min-1,检测波长为215 nm,柱温为室温.结果 本文方法可检出愈酚伪麻待因口服溶液中主药愈创木酚甘油醚的主要杂质游离愈创木酚,并能检出经氧化、酸、碱等破坏试验所产生的降解产物.结论 该法可用于愈酚伪麻待因口服溶液中有关物质的检查.     

愈创甘油醚片在健康人体中的药动学和生物等效性

目的研究愈创甘油醚片在健康中国人体内药动学和生物等效性。方法采用双周期交叉试验设计,20名健康男性受试者随机交叉单剂量口服愈创甘油醚片试验制剂和参比制剂0．2g,以高效液相色谱-质谱联用法测定人血浆中愈创甘油醚经时血药浓度,用DAS Ver2．0软件计算药动学参数,评价两制剂的生物等效性。结果愈创甘油醚片试验制剂和参比制剂的主要药动学参数ρmax分别为（909．3±314．7）和（874．1±301．5）μg·L^-1;tmax分别为（0．50±0．28）和（0．56±0．25）h;t1/2,分别为（1．54±0．92）和（1．53±1．08）h;AUC0→1分别为（1441-8±411．2）和（1486．9±482．8）μg·h·L^-1,AUC0→∞分别为（1456．5±418．2）和（1505．1±490．1）μg·h·L^-1;试验制剂的AUC0→1、AUC0→∞、ρmax的90％置信区间分别为参比制剂相应参数的91％-118％、91％-118％和94％-116％。以AUC0→t计算试验制剂中愈创甘油醚对参比制剂的相对生物利用度F为（99．7±15．1）％。结论经方差分析及双单侧t检验结果显示,试验制剂和参比制剂具有生物等效性。