抗组胺药非索非那定的研究进展

非索非那定是第二代H1抗组胺药,对H1受体有高度选择性,有直接的抗炎活性,起效快、作用维持时间长且长期使用不易出现耐药性.非索非那定的代谢动力学易受几种转运蛋白诱导剂或抑制剂的影响,但未见需调整剂量的报道,转运蛋白对非索非那定代谢的机理有待进一步的研究.临床用于治疗变态反应性疾病,如过敏性鼻炎、荨麻疹、过敏性哮喘、遗传性过敏性斑秃等,且联合其他药物疗效显著.目前,非索非那定微球的鼻内给药制剂正在研发中.非索非那定不良反应少见,无论是单独应用还是联合其他药物使用,都未见严重的心血管事件,不影响胆碱能活性.非索非那定不能透过血脑屏障、不进入中枢神经系统,被推荐于从事安全相关作业人员使用.     

盐酸非索非那定的合成

对甲基苯乙酸乙酯经甲基化、溴代和Sommelet反应、格氏反应、缩醛水解、还原胺化、水解后成盐制得盐酸非索非那定，总收率32％。     

非索非那定的微生物转化制备

研究了以普拉特链霉菌SIPI-76微生物转化特非那定为非索非那定的条件。考察碳源、氮源等培养基成分，底物的加入浓度、时间，生长细胞培养时的pH、温度、溶氧等参数对转化的影响。表明在优化条件下转化率达到90％。     

非索非那定短期治疗慢性荨麻疹疗效观察

慢性荨麻疹足一种常见病,治疗较困难,常规抗组胺药治疗效果常不理想.应用非索非那定短期治疗慢性荨麻疹取得一定效果,报告如下.     

非索非那定大鼠体内药代动力学研究

目的建立高效液相色谱法（HPLC）研究非索非那定灌胃给药后非索非那定体内药动学特点。方法采用HPLC测定,色谱柱为DikmaTMC18（4.6mm×250mm,5μm）,流动相：乙腈-0.5%磷酸二氢钾（pH3.8）-三乙胺（30∶70∶0.3）,流速：1.2ml/min,检测波长：220nm,检测非索非那定大鼠灌胃后药代动力学参数。结果非索非那定的药动学模型为二室模型,其药动学参数为Ka=1.689h-1,Cmax=1.225μg/ml,Tmax=1.8h,MRT=5.013h,t1/2α=1.018h。结论高效液相色谱法研究非索非那定大鼠灌胃给药后体内药代动力学,方法预处理简单、专属性强,结果可靠。     

特非那定合成工艺改进

特非那定是哌啶类抗组胺药，具有特异的外周H1受体拮抗作用，有抗5-羟色胺的作用，它是无中枢抑制作用、无镇静作用而高效安全的新型组胺受体H1拮抗剂，为目前临床上常用的抗过敏药物，主用于过敏性鼻炎，急慢性荨麻疹，枯草热的治疗。     

千金藤素对非索非那定肠吸收的影响

目的 研究千金藤素对非索非那定大鼠肠吸收的影响.方法 采用大鼠肠外翻模型,以维拉帕米为阳性对照,研究千金藤素对非索非那定肠吸收的影响,并用反相高效液相色谱法测定大鼠肠黏膜内外两测的非索非那定浓度.结果 非索非那定在大鼠十二指肠有吸收,千金藤素能增加非索非那定的吸收.结论 千金藤素能增加非索非那定吸收,机制可能是抑制了P...     

千金藤素对非索非那定肠吸收的影响

目的研究千金藤素对非索非那定大鼠肠吸收的影响。方法采用大鼠肠外翻模型,以维拉帕米为阳性对照,研究千金藤素对非索非那定肠吸收的影响,并用反相高效液相色谱法测定大鼠肠黏膜内外两测的非索非那定浓度。结果非索非那定在大鼠十二指肠有吸收,千金藤素能增加非索非那定的吸收。结论千金藤素能增加非索非那定吸收,机制可能是抑制了P-糖蛋白的外排。     

盐酸非索非那定杂质的LC-MS检测及结构鉴定

分别用HPLC和LC-MS法分析抗过敏药物盐酸非索非那定两年长期留存样品的杂质变化情况.结果发现3个杂质,主要杂质为α,α-二甲基-4-[4-[4-(羟基二苯甲基)-1-哌啶基]-1-氧代丁基]苯乙酸,两年留样后含量增加了1.53%其余两个杂质为α,α-二甲基-4-[1-羟基-4-[4-(羟基二苯甲基)-1-哌啶基]丁基]苯乙酸甲酯和α,α-二甲基-4-[1-羟基-4-[4-(羟基二苯甲基)-1-哌啶基]丁基]苯乙酸丁酯,含晕基本不变.     

HPLC测定大鼠非索非那定的血药浓度

目的建立大鼠血浆中非索非那定浓度的测定方法。方法采用HPLC法测定,色谱柱为DikmaTMC18柱(250 mm×4.6 mm,5μm),流动相为乙腈-0.5%磷酸二氢钾(pH3.8)-三乙胺(30:70:0.3),流速1.2 ml.min-1,检测波长220 nm。结果非索非那定0.098~7.000μg.ml-1线性关系良好(r=0.9997,n=7),高、中、低浓度测定的方法回收率为99.1%~104.5%。日内RSD为2.74%~6.67%,日间RSD为3.10%~6.98%。结论所建方法预处理简单?专属性强、灵敏度高,适合测定非索非那定的血药浓度。     

Fast Dissolving Tablets of Fexofenadine HCl by Effervescent Method

In the present work, fast dissolving tablets of fexofenadine HCl were prepared by effervescent method with a view to enhance patient compliance. Three super-disintegrants viz., crospovidone, croscarmellose sodium and sodium starch glycolate along with sodium bicarbonate and anhydrous citric acid in different ratios were used and directly compressible mannitol (Pearlitol SD 200) to enhance mouth feel. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity and in vitro dispersion time. Based on the in vitro dispersion time (approximately 20 s), three formulations were tested for in vitro drug release pattern in pH 6.8 phosphate buffer, short-term stability at 40°/75% RH for 3 mo and drug-excipient interaction (IR spectroscopy). Among the three promising formulations, the formulation ECP₃ containing 8% w/w of crospovidone and mixture of 24% w/w sodium bicarbonate 18% w/w of anhydrous citric acid emerged as the best (t_50% 4 min) based on the in vitro drug release characteristics compared to conventional commercial tablet formulation (t_50% 15 min). Short-term stability studies on the formulations indicated that there are no significant changes in drug content and in vitro dispersion time (P<0.05).     

千金藤素对大鼠体内非索非那定药动学的影响

目的研究千金藤素对大鼠体内非索非那定药动学的影响。方法SD大鼠10只随机分为两组,分别灌胃给予非索非那定、千金藤素+非索非那定,不同给药时间采集血样。采用高效液相色谱法测定非索非那定血药浓度,绘制药物浓度 时间曲线,用3P97药动学软件拟合药动学参数,并进行统计分析。结果非索非那定和千金藤素+非索非那定组Cmax分别为（1.225±0.770）,（1.417±0.440） μg&#8226;mL 1 （P＜0.05）;AUC0 t分别为（5.379±1.570）,（8.088±1.760） mg&#8226;h&#8226;L 1（P＜0.01）。千金藤素＋非索非那定组AUC0 t和Cmax分别增加7.09%（P＜0.05）和15.67%（P＜0.05）;两组Ka、 MRT和t1/2差异无统计学意义。结论与千金藤素合用后,非索非那定在大鼠体内的生物利用度增加,千金藤素对非索非那定在大鼠体内药动学具有显著影响。     

HPLC法测定盐酸非索非那定缓释微丸胶囊的含量

目的：建立以高效液相色谱法测定盐酸非索非那定缓释微丸胶囊中盐酸非索非那定含量的方法。方法：以Kromasil C_（18_（250 mm×4.6 mm,5μm）为色谱柱,流动相为乙腈-0.5%磷酸二氢钾溶液（以磷酸调节pH至4.0）（55：45）,检测波长为210 nm,流速为1.0 ml·min~（-1）,柱温为35℃,进样量为20μl。结果：盐酸非索非那定在30.23~302.30μg·ml~（-1）范围内线性关系良好（r=0.999 7）,平均回收率为99.75%,RSD=0.1%（n=6）。结论：本方法简便、准确、专属性强,可用于该制剂的含量测定。     

Fexofenadine in pediatrics: oral tablet and suspension formulations

Allergic rhinitis is a common chronic condition in children. Oral antihistamines are a first-line treatment option in allergic rhinitis and different formulations are available to aid administration to children. The tablet formulation of the second-generation antihistamine fexofenadine has established efficacy and safety in both adults and children. To aid administration in young children, a new oral suspension formulation of fexofenadine has been developed, indicated for the relief of seasonal allergic rhinitis symptoms in children aged 2-11 years and for uncomplicated skin manifestations of chronic idiopathic urticaria in children aged 6 months-11 years. Clinical studies have shown the oral suspension to have both bioequivalence with the 30 mg tablet formulation and a favorable safety and tolerability profile.     

Fexofenadine: new preparation. Terfenadine, without cardiotoxicity

(1) Fexofenadine, a non anticholinergic non sedative antihistamine, is available in France for oral treatment of allergic rhinitis and chronic urticaria. (2) Fexofenadine is actually an active metabolite of terfenadine, a drug taken off the market because of its cardiotoxicity. (3) In seasonal allergic rhinitis a comparative trial showed that the effect of fexofenadine (120 mg/day in a single intake) was moderate and not different from that of cetirizine. (4) In chronic urticaria a dose-finding study showed that the optimal oral dose of fexofenadine was 180 mg/day. The lack of comparative trials means that the efficacy of fexofenadine in relation to other antihistamines is not known. (5) Fexofenadine seems to be well tolerated. Animal studies and limited clinical experience have failed to detect any cardiotoxicity.