非索非那定的合成

α,α-二甲基苯乙酸经硅胶负载磷钨酸(PW/SiO2)固体酸催化酯化、与4-氯丁酰氯反应生成α,α-二甲基-4-(4-氯-1-氧代丁基)苯乙酸乙酯,用硼氢化钠还原后与α,α-二苯基-4-哌啶甲醇反应、碱性水解制得抗组胺药非索非那定,总收率约48%.     

特非那丁不良反应概况及在我国的应用前景

特非那丁做为第一个非镇静性Ｈ1受体阻滞剂,1982年首先在英、法、西德上市,1985年美国获准上市,1989年我国扬州制药厂以试字号上市。至1997年1月14日,美国ＦＤＡ做出了建议特非那丁从美国市场上撤销的决定以来,已在国际市场上存在达15年之久[1]。美国ＦＤＡ做出决定之后,世界各国都相应地做出了反应,对我国的市场也产生了巨大的影响,现将我们检索特非那丁的不良反应情况及我国的现状报告如下。1　产生背景特非那丁是从抗精神病药物的筛选中发现的,构效关系研究及一系列的药理临床试验结果却表明,它是一个无中枢抑制作用的特异性的外周Ｈ1受…     

特非那定的临床不良反应分析

特非那定 (叔呱丁醇、敏迪 )选择性地阻断组胺 H1受体,具有良好的抗组胺作用,无镇静及抗胆碱作用,作用持久,广泛应用于过敏性鼻炎、荨麻疹及过敏性皮肤病的治疗。本药临床不良反应时有报道,尤以心血管系统、消化系统、中枢神经系统、药疹为多。本文就 1994年至今国内文献报道的特非那定片不良反应 14例进行分析。 1心血管系统 [1～ 5]　　心血管不良反应 5例患者 (占 35． 71％ )中,完全性右束支传导阻滞 1例,阵发性室性心动过速 2例,扭转型室性心动过速 2例;患者均为女性,年龄 23～ 40岁;因荨麻疹、药疹、足癣、阴道炎等服用特…     

新型非镇静性抗组胺药特非那丁

特非那丁是一种安全性高的外周H_1受体拮抗剂,用来治疗变应性鼻炎,过敏性皮肤疾病等症。由于不通过血脑屏障,无中枢抑制作用,因而不产生嗜睡,倦怠等副反应。本文综述了它的药理、毒理、药物动力学和临床等方面的研究进展。     

特非它唑的合成

从中间体4-(4-溴丁酰基)苯基-a，a-二甲基乙氰开始，经缩合、还原、环化三步合成特非它唑，收率11％。     

特非那定致荨麻疹1例

【病例】女 ,37ａ ,因洗澡后皮肤瘙痒自服特非那定 (商品名 :敏迪 ,江苏联环药业股份有限公司 ,批号2 0 0 10 90 1) 6 0ｍｇ ,1ｈ后双腿内侧皮肤瘙痒加剧 ,随手抓处起风团 ,高出皮肤。ｄ 2到医院就诊 ,医师未考虑是该药引起的过敏 ,随即开了特非那定 (生产厂家同上 ) 6 0ｍｇ ,ｐｏ ,ｂｉｄ ,维生素Ｃ 30 0ｍｇ ,ｐｏ ,ｔｉｄ。 30ｍｉｎ后两下肢风团加重 ,并融合成片。瘙痒难忍 ,并逐渐向上漫延至全身 ,此时患者呼吸急促 ,心律加快。经查 :ｔ 37 2℃ ,Ｐ 96ｂｅａｔｓ·ｍｉｎ- 1,Ｒ 2 4ｂｅａｔｓ·ｍｉｎ- 1,ＢＰ90 /140ｍｍＨｇ(1ｍｍ…     

苯甘氨酸合成工艺的改进

本文介绍了一种合成苯甘氨酸的新方法,即以苯甲醛、氨仿生主要原料经过相转移催化缩合、环合再水解制成苯甘氨酸。收率可达８０％,结果表明,此路线简便易行。     

门诊不合理处方分析与预防措施

摘要：目的 了解门诊处方用药情况,为促进医院合理用药提供参考。方法：抽取我院2011年1-3月的门诊处方300张,按照《医院处方点评管理规范(试行)》及《处方管理办法》对不合理处方进行分析。结果：不合理处方占所调查处方的26%;主要体现在处方书写不规范、用药指证不明确、用法用量不适宜、联合用药不适宜、重复用药等方面。结论：我院门诊处方用药情况基本合理,但处方质量仍有待提高。针对不合理处方存在的问题制定相应预防措施,确保用药安全、有效、经济。     

Population Pharmacokinetics of Terfenadine

Purpose. After oral administration of terfenadine, plasma concentrations of the parent drug are usually below the limits of quantitation of conventional analytical methods because of extensive first-pass metabolism. Data are usually reported on the carboxylic acid metabolite (Ml) but there are no published reports of pharmacokinetic parameters for terfenadine itself. The present study was undertaken to evaluate the population pharmacokinetics of terfenadine. Methods. Data from 132 healthy male subjects who participated in several different studies were included in this analysis. After an overnight fast, each subject received a single 120 mg oral dose of terfenadine; blood samples were collected for 72 hours. Terfenadine plasma concentrations were measured using HPLC with mass spectrometry detection and Ml plasma concentrations were measured using HPLC with fluorescence detection. A 2-compartment model was fitted to the terfenadine data using NONMEM; terfenadine and Ml data were also analyzed by noncompartmental methods. Results. Population mean Ka was 2.80 hr^–1, T_lag was 0.33 hr, Cl/F was 4.42 × 10³ 1/hr, V_C/F was 89.8 ×10³1, Q/F was 1.85 ×10³ 1/hr and V_p/F was 29.1 × 10³1. Intersubject CV ranged from 66 to 244% and the residual intrasubject CV was 21%. Based on noncompartmental methods, mean terfenadine C_max was 1.54 ng/ml, T_max was 1.3 hr, t_{1/2 Z} was 15.1 hr, Cl/F was 5.48 × 10³ 1/hr and V_z/F was 119.2 × 10³1. Ml concentrations exceeded terfenadine concentrations by more than 100 fold and showed less intersubject variability. Conclusions. Terfenadine disposition was characterized by a 2-compartment model with large intersubject variability, consistent with its significant first-pass effect.     

贝诺酯合成的工艺改进

目的：探索贝诺酯的最佳合成工艺。方法：在合成乙酰水杨酰氧时以DMF为催化剂,然后用聚乙二醇（PEG）为相转移催化剂酯化而得贝诺酯。结果：合成了贝诺酯,总收率为95％。结论：此方法缩短了时间,提高了产率,降低了成本。     

Terfenadine, a nonsedating antihistamine

Terfenadine is an antihistamine recently approved for use in the U.S. Terfenadine possesses a unique chemical structure when compared with other antihistamines. It is a selective inhibitor of H1-receptors with little or no anticholinergic, antiserotoninergic, or antiadrenergic effects. Comparative studies have shown that terfenadine is as effective as other antihistamines in the treatment of allergic rhinitis and other hypersensitivity conditions. This drug produces a minimal amount of central nervous system (CNS) depression, which is documented by studies demonstrating that terfenadine and its metabolites do not readily pass into the CNS and have little affinity for central H1-receptors. The lack of CNS depression and anticholinergic effects, and the long duration of action that allows twice-a-day dosing make terfenadine an attractive alternative to other antihistamines.     

卡巴拉汀的合成方法改进*

目的:研究卡巴拉汀的合成新工艺。方法:以间羟基苯乙酮为原料,经Leuckart反应一步合成中间体3-(1-(二甲基氨基)乙基)苯酚,然后再与甲乙氨基甲酰氯缩合合成卡巴拉汀。结果:反应路线缩短,两步收率为74%。结论:本方法提高了收率,操作简单,适合于工业化生产。     

特非那定分散片治疗荨麻疹

目的：临床验证特非那定分散片治疗过敏性疾病的疗效。方法：６０例荨麻疹病人，男性２５例，女性３５例；年龄３４±ｓ１３ａ；病程７±２２ｍｏ；随机分特非那定分散片组及寻常片组各３０例，均６０ｍｇ，ｐｏ，ｂｉｄ，共７ｄ。结果：分散片治疗总有效率９０％，寻常片８３％（Ｐ＜０．０５）；服药后１ｈ起效率，分散片为９２％，寻常片０；不良反应发生率２组相似。结论：特非那定分散片治疗荨麻疹的疗效及起效时间优于寻常片。     

法西多曲合成工艺的改进

目的:对法西多曲合成工艺改进.方法:以胡椒丙烯酸为原料,经加成、拆分、缩合反应以及结晶分离,制得法西多曲.结果:合成目标化合物,总收率39.2%.结论:该方法操作简单,收率较高.