反相高效液相色谱法测定人血浆中萘普生含量

目的：建立ＲＰ－ＨＰＬＣ测定人血浆中萘普生含量的方法，研究该药在人体内药物动力学。方法：血浆在酸性介质中以氯仿提取，Ｃ１８色谱柱，２３０ｎｍ波长紫外检测，以甲基炔诺酮为内标，流动相为甲醇∶水（６５∶３５，预先用磷酸调至ｐＨ３．０～３．１）；所得药时数据采用ｍｉｎｉｍ３．０８程序拟合计算药动学参数。结果：萘普生血药浓度在０．１～２００μｇ·ｍｌ－１范围内与色谱峰高比呈线性关系，ｒ＝０．９９９９（ｎ＝８）。４名健康受试者单剂量口服５００ｍｇ萘普生片后，药时曲线呈一室模型。Ｃｍａｘ＝７３．６±８．３μｇ·ｍｌ－１，Ｔｍａｘ＝２．３±０．５ｈ，Ｔ１／２Ｋｅ＝９．７±３．５ｈ，Ｋｅ＝０．０８±０．０４ｈ－１，ＡＵＣ０→２４＝８２０．０±８５．７μｇ·ｈ·ｍｌ－１。结论：本法简单、快捷、灵敏，能满足药动学研究的需要     

萘普生肠溶胶囊人体药物动力学和相对生物利用度

目的：测血药浓度，３Ｐ８７药动学程序进行药物动力学参数模拟，双单侧检验法作生物等效性判别。方法：８名健康男性志愿者交叉服用萘普生肠溶和胃溶胶囊各５００ｍｇ，以ＨＰＬＣ法测定。结果：药－时曲线符合一级吸收二室模型，萘普生肠溶胶囊的主要药动学参数分别为Ｋａ０．７５±０．２８ｈ－１，ＡＵＣ１５３３．０±２１７．６μｇ·ｈ·ｍｌ－１，Ｔｍａｘ３．６±１．６ｈ，Ｃｍａｘ７８．１±１４．１μｇ·ｍｌ－１。结论：胃溶胶囊的药动学参数与肠溶胶囊的药动学参数相似，肠溶胶囊的相对生物利用度为１０４．０１％。     

高效液相色谱法测定软膏中曲安萘德和水杨酸含量

目的：建立一种快速的用高效液相色谱法测定曲安萘德（ＴＡ）和水杨酸（ＳＡ）的含量。方法：使用Ｃ１８色谱柱,流动相为甲醇∶水（６０∶４０Ｖ／Ｖ）,检测波长为２４０ｎｍ及２９０ｎｍ。结果：方法在７ｍｉｎ内完成测定,其中水杨酸在８～２４μｇ·ｍｌ－１浓度范围内,ｒ＝０．９９９５,ＲＳＤ＝０．４９％,回收率为９９．７％～１００．３％;曲安萘德在６．２５～５０μｇ·ｍｌ－１浓度范围内,ｒ＝０．９９９８,ＲＳＤ＝０．４７％,回收率为９９．４％～９９．８％。结论：方法可行快速准确地检测软膏中的曲安萘德和水杨酸含量     

萘普生肠溶胶囊人体药物动力不和相对生物利用度

测血药浓度，３Ｐ８７约动学程序进行药物动力学参数模拟，以单侧检验法作主物等效性判别。方法：８名健康男性示愿者交叉服用萘普生肠溶和胃溶胶囊各５００ｍｇ，以ＨＰＬＣ法测定。结果：药－时曲线符合一级吸收二室模型，萘普生肠溶胶囊的主要药动学参数分别为Ｋａ０．７５０．２８ｈ＾－１，ＡＵＣ１５３３．０±２１７．６μｇ．ｍｌ＾－１，Ｔｍａｘ３．６±１．６ｈ，Ｃｍｑｘ７８．１±１４．１μｍｌ＾－１。     

高效液相色谱法测定清消口服液中绿原酸的含量

目的：建立一种测定清消口服液中绿原酸含量的方法。方法：ＲＰＨＰＬＣ法。采用ＨｙｐｅｒｓｉｔＣ１８柱（５μｍ,３．９×１５０ｍｍ）,甲醇水冰醋酸（１７∶１８０∶３．１）为流动相,流速１．４ｍｌ·ｍｉｎ－１,紫外检测波长３２７ｎｍ。结果：线性范围０．０６４～１．２８μｇ,ｒ＝０．９９９５,回收率在９９％以上。结论：本法测定清消口服液中绿原酸的含量,操作简便,结果准确。     

荧光法测定胶囊中萘普生的含量

根据萘普生在碱性介质中的内源荧光，提出用直接荧光法测定萘普生胶囊的含量，线性范围为 ０．２～１４．０μｇ·ｍＬ~－１．     

萘普生分散片中赖氨酸的含量测定

目的：建立萘普生分散片中赖氨酸含量测定的方法。方法：用紫外分光光度法,测定波长为５６５ｎｍ。结果：平均回收率为９９．２９％,ＲＳＤ为０．２１％（ｎ＝１０）。线性范围为１．７９２￣８．９６４μｇ／ｍｌ。结论：该方法准确、可行。     

高效液相色谱法测定布替萘芬乳膏的含量

建立布替萘芬乳膏的含量测定方法。方法：用高效液相色谱法,乳膏用甲醇超声提取Ｈｙｐｅｒｓｉｃ Ｃ１８柱１５０ｎｍ＊４．６ｍｍ,５μｍ,流动相为甲醇－０．０５ｍｏｌ．Ｌ＾－１醋酸铵溶液（９５：５）,流速０．８ｍｌ．ｍｉｎ＾－１,检测波长２２３ｎｍ。结果：布替萘芬在０．０９－０．４５ｇ范围内呈良好的线性关系,平均回收率９８．９％,ＲＳＤ１．７％,测得３批样品的标准量均在（９０－１１０）％之间。结论本法简     

萘普生控释片的人体相对生物利用度的研究

目的：研究８名健康志愿者口服萘普生片剂的药代动力学特征。方法：ＨＰＬＣ内标法测定人血浆中萘普生浓度，该法回收率＞８０％，日内及日间变异系数均＜１０％。结果：萘普生控释片与普通片的Ｔｍａｘ分别为８．３８±４．１４和２．３１±１．５１ｈ，Ｃｍａｘ分别为３７．１±５．８和５６．５±１０．１ｍｇ·Ｌ－１，ＭＲＴ分别为２０．５±１．７８和１６．５±１．１５ｈ，经检验差异均有显著性（Ｐ＜０．０５）；两制剂的ＡＵＣ０～４８分别为１０７１．１±１０６．１和１０２２．３±１１６．６ｍｇ·ｈ·Ｌ－１，控释片相对于普通片的生物利用度为１０５．３％±９．２２％，差异无统计学意义（Ｐ＞０．０５）。结论：该控释片具有明显的控释特征和临床使用价值。     

头孢他啶及有关物质的HPLC测定

采用Ｓｈｉｍ－ＰａｃｋＯＤＳ柱，以三乙胺醋酸溶液—水—乙腈（６９２４７０）（ｐＨ４．９）为流动相，流量１．０ｍｌ／ｍｉｎ，室温操作，检测波长２５４ｎｍ，在对头孢他啶及各有关物质作ＨＰＬＣ分离的同时，分别测定头孢他啶与吡啶的含量。线性范围分别为：５０～１５０ｍｇ／ｍｌ（ｒ＝１．００００）；０．５～１２．５μｇ／ｍｌ（ｒ＝０．９９８７）。ＲＳＤ分别为０．５％、３．４％。吡啶最低检测限：３．５ｎｇ。方法简便，准确     

萘普生合成路线概述

采用Friedel-Crafts反应通过6-甲氧基-2-乙酰萘、6-甲氧基-2-丙酰萘或经羧烷基化和氯甲基化合成萘普生消旋体及其拆分的进展,结合国内情况作了评述。     

Diflunisal compared with naproxen in the treatment of osteoarthrosis of hip or knee: a double-blind trial

Summary

A randomized double-blind trial was carried out in 20 patients with osteoarthrosis of the hip or knee to compare the efficacy and tolerance of treatment with diflunisal or naproxen. During the first 4 weeks, patients received either 250?mg diflunisal or 250?mg naproxen twice daily and this was increased by 250?mg daily in 5 patients on diflunisal and in 3 on naproxen for the second 4 weeks of the trial. The results of subjective assessments made before and at the end of Week 8 showed a trend in favour of diflunisal for improvement of symptoms, except for weight-bearing pain which was improved in only 1 patient in each group. More of the patients receiving diflunisal than naproxen considered treatment to have been satisfactory, and rated their response as equally as good as or better than previous medication. Diflunisal produced significantly fewer side-effects than naproxen, the use of which was associated with a relatively high incidence of gastro-intestinal upsets, leading to the withdrawal of 2 patients at Week 4.     

萘普待因的镇痛效应和急性毒性作用

目的··:评价萘普待因 (可待因与萘普生的比例为1 10)的镇痛作用。方法··:镇痛作用采用大小鼠醋酸扭体法和甩尾法 ,急性毒性作用采用一次给药观察7d的试验方法。结果··:大、小鼠醋酸扭体的半数有效量 (ED50)值分别为1.49和4.96mg·kg -1 ,甩尾法的ED50 值分别为0.34和0.67g·kg-1 ,都表现出明显的镇痛作用和量效关系。半数致死量 (LD50)值大、小鼠分别为0.31和1.78g·kg-1。结论··:萘普待因具有较好的镇痛作用和量效关系 ,而且可待因和萘普生在复方中表现出较好的镇痛协同作用 ,但毒性并没有加强     

萘普生钠的人体药动学及相对生物利用度

目的 :对萘普生钠的两种制剂进行生物等效性评价。方法 :本实验采用高效液相色谱法测定了 18名健康男性志愿受试者随机交叉单剂量口服萘普生钠颗粒剂 (受试制剂 )和胶囊 (参比制剂 )后的不同时刻血浆中萘普生钠的浓度。依据测定数据 ,计算萘普生钠两种制剂的药动学参数及受试制剂的相对生物利用度。结果 :18名健康受试者口服受试制剂和参比制剂后 ,血浆中萘普生钠的Tmax分别为 (1.1± 0 .6 )和 (1.3± 0 .8)h ;Cmax分别为 (36 .1± 7.6 )和 (40 .6± 8.9)mg·L-1;t1/2 分别为(15 .9± 2 .5 )和 (15 .5± 2 .2 )h ;AUC0～t分别为 (499.6± 118.2 )和 (5 39.9± 12 6 .9)mg·h·L-1;AUC0→∞ 分别为 (5 5 9.5± 132 .4 )和 (6 6 7.2± 15 5 .6 )mg·h·L-1。受试制剂的相对生物利用度 (94 .8± 13.1) %。以上参数统计学分析结果表明两种制剂差异无显著性。结论 :萘普生钠两种制剂体内生物作用等效     

Synthesis of deuterated naproxens

A general scheme for the synthesis of (S)‐6‐methoxy‐2‐propanoic acid (naproxen) deuterated on the naphthyl ring, methoxy group, or both, is described. The resulting labeled naproxen derivatives are useful probes for examining atypical kinetics displayed by cytochrome P450 2C9. Copyright © 2007 John Wiley & Sons, Ltd.     

dl—萘普生的电还原法合成工艺研究

应用电还原合成方法,从2－萘甲醚（2）出发3步合成dl－萘普生,工艺路线简单,反应条件温和,总收率为40％。     

萘普生脉冲释药片的研制及体外释药影响因素考察

目的:制备萘普生脉冲释药片并考察体外释放的影响因素。方法:以乙基纤维素和丙烯酸树脂Ⅱ号为包衣材料制备包衣片,通过体外释放度的测定来考察片芯及包衣材料等因素对脉冲释药片体外释放的影响。结果:崩解剂的用量、包衣液中致孔剂的含量及包衣膜的厚度为影响药物体外释放的主要因素。结论:萘普生脉冲释药片在体外具有脉冲释药特性。     

PARTIAL-AREA METHOD IN BIOEQUIVALENCE ASSESSMENT: NAPROXEN

Regulatory authorities require demonstration of bioequivalence through comparisons of different pharmacokinetic parameters, the area under the plasma concentration–time curve (AUC), the maximum plasma concentration (C_max), and the time to reach peak concentration (T_max). The applicability and validity of regulatory requirements have been widely criticized on statistical and clinical relevance grounds. For most noncomplicated absorption models, the AUC correlates well with the extent of absorption. However, in nonlinear models of absorption, in mechanisms involving recycling of drugs, and for drugs with long half-life, the use of total AUC (from zero to infinity) can give erroneous and clinically irrelevant results since the area is mostly determined by elimination phase or by recycling. The calculation of total AUC also involves prolonged sampling, adding to the cost and risks associated with bioequivalence studies. The use of C_max or T_max as a measure of rate of absorption, to correlate with clinical relevance, is widely criticized on logical, technical, and statistical grounds. For drugs used on a multiple-dose basis, C_max and T_max evaluations become redundant since the average plateau concentration is not affected by these parameters. To resolve the drawbacks in the traditional methodology of bioequivalence evaluation, the use of partial areas in lieu of total AUC, T_max, and C_max is suggested. This study investigates the logic and robustness of the partial-area method in establishing bioequivalence. We conclude that the 5 h AUC is a more relevant parameter to establish naproxen bioequivalence than AUC_inf. We recommend against using symmetrical confidence intervals and report excellent agreement among several methods of calculating confidence intervals, probability values, and nonparametric tests. We suggest that a single-point short-term AUC is a better indicator of the bioequivalence of generic products than the total AUC, C_max, and T_max as required currently by the regulatory authorities. © 1997 by John Wiley & Sons, Ltd.