Medication-induced oesophageal injury leading to broncho-oesophageal fistula

Medication-induced oesophageal injury is one of the least recognised side-effects of oral medication and, in contrast to other oesophageal pathologies, is rarely considered in the differential diagnosis of chest pain. We describe a case of medication-induced oesophageal injury with a rare complication in which the diagnosis was not considered until the characteristic features were demonstrated at endoscopy.


     

阿西美辛缓释片的研制及释药因素考察

目的:制备阿西美辛缓释片并对释药因素进行考察.方法:采用湿法制粒工艺,以羟丙基甲基纤维素(HPMC)为骨架材料,制备阿西美辛缓释片;运用正交设计法筛选确定速释部分的处方;对HPMC规格和用量、润湿剂浓度、制片压力等影响释药的因素进行考察,并在此基础上进行处方的筛选.结果:阿西美辛缓释片的体外释药行为符合Higuchi方程,HPMC用量、润湿剂浓度、制片压力对释药几乎无影响,而HPMC规格对药物的释放产生一定的影响.结论:采用HPMC作为基本骨架材料,结合其他辅料,可制备日服1次的阿西美辛缓释片.     

人血浆中阿西美辛及其代谢物吲哚美辛的固相萃取—HPLC—UV法测定

以氟比洛芬为内标，采用固相萃取－紫外检测的HPLC法同时测定人血浆中阿西美辛和吲哚美辛，灵敏度和选择性均高，最低定量限为20ng/ml，线性范围为20－1000ng/ml，血浆内源物质不干扰测定。     

阿西美辛涂膜剂体外透皮吸收的影响因素考察

目的:研究阿西美辛涂膜剂体外透皮吸收的影响因素,实验观察促透剂种类、浓度以及pH值对体外透皮吸收的影响.方法:采用Franz扩散池,以小鼠的离体皮肤为屏障,紫外分光光度法测定接受液中阿西美辛的含量,计算一定时间内其单位面积累积透皮吸收量(Q).结果:用抛物线拟合法建立不同时间、不同pH值及不同促透剂浓度对阿西美辛透皮吸收量的数学模型,并计算得出最佳吸收pH值为6.35,月桂氮(艹卓)酮(azone)的最佳浓度为5.7%,月桂氮(艹卓)酮和丙二醇(PG)联合使用时,丙二醇的最佳浓度为3.85%.结论:本实验确立的阿西美辛涂膜剂有良好的透皮吸收作用.     

Non-steroidal anti-inflammatory drugs that cause relatively little gastric damage

Abstract Gastrointestinal damage by non-steroidal anti-inflammatory drugs (NSAID), which is common and sometimes fatal, involves inhibition of prostaglandin (PG) synthesis. The damage is less with NSAID that inhibit inflammatory cyclo-oxygenase (COX)-2 but not gastroprotective COX-1. We have compared nimesulide and acemetacin, two NSAID that cause relatively little gastric damage, with indomethacin for effects on purified COX-1 and COX-2. The results are related to findings on human gastric mucosa and leucocytes. With purified COX-1, inhibition was absent with nimesulide, weak with acemetacin (inhibitory concentration of 50% [IC₅₀] 85 m?mol/L), and potent with indomethacin (IC₅₀ 0.6 m?mol/L). Inhibition of purified COX-2 occurred with nimesulide and indomethacin (IC₅₀ values 90 and 4.1 m?mol/L, respectively) but not acemetacin. All results with nimesulide are consistent with a preferential block of COX-2 that contributes to relatively little gastric damage in patients. However, our previous report on acemetacin needs re-evaluation. Acemetacin did not inhibit sheep COX-2 and only weakly inhibited COX-1. Our previous leucocyte (COX-2) experiments required 24 h incubation, and hydrolysis of acemetacin to indomethacin presumably accounted for the COX-2 inhibition. In the few minutes of enzyme incubation, virtually no hydrolysis would be expected. Acemetacin itself presumably causes relatively little gastric damage mainly because it only weakly inhibits COX-1.     

阿西美辛脂质体凝胶剂的研制

目的研制阿西美辛脂质体凝胶剂,并进行评价.方法采用不同方法、不同药-脂比处方制备脂质体,然后对其包封率进行比较,从而优选出最佳制备方法与最佳处方,并进一步制备成脂质体凝胶剂;采用HPLC测定制剂中阿西美辛的含量,葡聚糖凝胶柱结合HPLC测定制剂中阿西美辛的包封率;考察了制剂的皮肤刺激性与初步稳定性.结果制剂的含量控制在0.09%～0.110%范围之内;平均包封率为(58.76±12.47)%;无皮肤刺激性;不易高温贮存,对光不稳定.结论经初步评价,所制备的阿西美辛脂质体制备方法可行、简便、质量稳定.     

RP—HPLC法测定阿西美辛缓释片体内活性代谢物吲哚美辛的血药浓度

目的 :建立一种新的RP -HPLC法测定阿西美辛缓释片活性代谢物吲哚美辛的血药浓度。方法 :提取溶剂为 1,2 -二氯乙烷。色谱条件 :C18反相柱 ,流动相为 0 0 2mol·L-1磷酸二氢钾溶液 -甲醇 (71∶2 9,用磷酸调至pH为 4 2 ) ,流速 :1 0mL·min-1,检测波长 :2 5 4nm ,内标为 10 μg·mL-1的萘普生甲醇溶液。结果 :检测浓度在 0～ 1 2 μg·mL-1范围内阿西美辛体内的活性代谢物吲哚美辛的峰面积与浓度有良好的线性关系 ,回归方程 :A =0 0 12 95 0 5 0 2 2 3C ,r =0 9991(n =7) ,日内RSD为 1 8%～ 6 5 % (n =6 ) ,日间RSD为 2 4%～ 5 7% (n =5 ) ,平均方法回收率为 97 74%～ 98 88% ,RSD <13 % (n =5 ) ,平均提取回收率为 81 97%～ 84 33% ,RSD <9% (n =5 )。结论 :本法结果准确 ,灵敏度高 ,重现性好。     

Mechanisms underlying the anti-inflammatory activity and gastric safety of acemetacin

BACKGROUND AND PURPOSE: Acemetacin is regarded as a pro-drug of indomethacin and induces significantly less gastric damage but the reasons for this greater gastric safety of acemetacin are unclear. The anti-inflammatory effects of acemetacin have been attributed, at least in part, to its hepatic biotransformation to indomethacin. The aim of this study was to determine the effects of acemetacin and indomethacin in an in vivo model of acute inflammation and to examine the importance of biotransformation of acemetacin (to indomethacin) to its anti-inflammatory actions. EXPERIMENTAL APPROACH: The zymosan airpouch model was used in rats. Indomethacin or acemetacin (2.7-83.8 micromol kg(-1)) were administered orally or directly into the pouch. Leukocyte infiltration, prostaglandin (PG) E(2) and leukotriene (LT) B(4) levels in exudates, and whole blood thromboxane (TX) B(2) synthesis were measured. KEY RESULTS: Acemetacin was rapidly converted to indomethacin after its administration. Both acemetacin and indomethacin elicited comparable, dose-dependent reductions of leukocyte infiltration and of PGE(2) and TXB(2) synthesis. However, indomethacin induced more gastric damage than acemetacin and elevated LTB(4) production in the airpouch. CONCLUSIONS AND IMPLICATIONS: The similar effects of acemetacin and indomethacin on leukocyte infiltration and PG synthesis are consistent with rapid biotransformation of acemetacin to indomethacin. Some of this biotransformation may occur extra-hepatically, for instance in inflammatory exudates. Acemetacin probably exerts actions independent of conversion to indomethacin, given the different effects of these two drugs on LTB(4) production. Such differences may contribute to the relative gastric safety of acemetacin compared to indomethacin.     

单剂量口服国产和进口阿西美辛胶囊的生物等效性

目的 :评价国产和进口阿西美辛 (AC)胶囊的生物等效性。方法 :采用双交叉试验设计 ,2 4名健康受试者随机接受单剂量口服参比制剂或试验制剂 90mg ,清洗期 7d ;采用固相萃取 HPLC UV法测定AC及其代谢物吲哚美辛 (ID)的血药浓度。cmax,tmax采用实测值 ,梯形法计算AUC ,双单侧t检验法用于生物等效性检验。结果 :国产AC胶囊的相对生物利用度以AC计算 (98 35± 10 35 ) % ,以ID计算 (10 1 46± 10 5 7) % ,经方差分析及双单侧t检验表明两者具有生物等效性。结论 :进口和国产AC胶囊具生物等效性