头孢氨苄缓释片和普通胶囊的多剂量生物利用度和药物动力学比较

目的：比较头孢氨苄（ＣＥＸ）缓释片和普通胶囊的多剂量生物利用度和药物动力学。方法：１０例健康志愿者随机交叉口服ＣＥＸ缓释片５００ｍｇ，ｑ１２ｈ，ＣＥＸ普通胶囊２５０ｍｇ，ｑ６ｈ，服药３ｄ达稳态后进行波动试验和稳态药物动力学研究，ＨＰＬＣ法测定血药浓度。结果：ＣＥＸ缓释片Ｃｓｍａｘ，Ｃｓｍｉｎ和波动系数（ＦＩ）分别为１０．７±１．９μｇ／ｍＬ，０．６９±０．１４μｇ／ｍＬ和１．７５±０．０６；Ｔｍａｘ，Ｃｍａｘ，ＡＵＣ分别为３．１±０．７ｈ，９．９±１．２μｇ／ｍＬ，５０±１１ｈ·μｇ／ｍＬ。缓释片Ｔｍａｘ较普通胶囊明显延长（Ｐ＜０．０１），Ｃｍａｘ和ＡＵＣ与普通胶囊相比无显著性差异（Ｐ＞０．０５）。结论：ＣＥＸ缓释片达峰时间延长，维持有效血药浓度的时间较长。     

多剂量口服5-单硝酸异山梨酯缓释片及普通片的药代动力学和生物利用度研究

对１０名健康男性受试者连续６ｄ多剂量交叉ｐｏＩＳ５ＭＮ缓释片和普通片的药代动力学性质和相对生物利用度进行了研究。结果表明：ＩＳ５ＭＮ缓释片和普通片的Ｔｍａｘ分别为５０ｈ和１４ｈ（Ｐ＜００５），前者的缓释效果十分明显；ＡＵＣ经对数转换后的多种统计分析表明，ＩＳ５ＭＮ缓释片（４０ｍｇ）与ＩＳ５ＭＮ普通片（２０ｍｇ×２）生物等效；ＩＳ５ＭＮ缓释片的相对生物利用度为１０８９５％；ＩＳ５ＭＮ缓释片和普通片的Ｃｍｉｎ分别为７４２０ｎｇ·ｍｌ－１和１３４４２ｎｇ·ｍｌ－１（Ｐ＜００５），而两种制剂的其他药代动力学参数如Ｃｍａｘ，ＡＵＣ２４０，ＡＵＣ∞０，Ｋｅ，Ｔ１／２以及波动系数（ＦＩ）等均无显著性差异（Ｐ＜００５）。多次给药后两种制剂都无明显的蓄积。     

盐酸地尔硫Zou与卡马西平在家兔体内的相互作用

本文采用荧光偏振免疫分析（ＦＰＩＡ）法测定卡马西平血药浓度，高效液相色谱分析（ＨＰＬＣ）法测定地尔硫Ｚｏｕ血药浓度，研究在六只家兔体内两药的相互作用。结果表明地尔硫Ｚｏｕ能显著升高卡马西平血药浓度，使其平均峰浓度（Ｃｍａｘ），药－时曲线下在（ＡＵＣ），消除半衰期（Ｔ１／２β）分别增加７０．５％，９０．２％，５７．３％，清除率（Ｃ１）下降５５．４％。上述参数在单，合用药间的差异具有统计学意义（Ｐ＜０     

两种布洛芬缓释制剂的药物动力学与相对生物利用度

目的：考察两种布洛芬缓释剂芬尼康止痛消炎片与芬必得胶囊达稳态后，血清中布洛芬的药物动力学与相对生物利用度。方法：采用反相高效液相色谱法分别测定１８名健康志愿受试者一日两次分别口服芬尼康６００ｍｇ与芬必得６００ｍｇ达稳态后，布洛芬的血药浓度变化情况，计算药物动力学参数与相对生物利用度，并以配对ｔ检验与双单侧ｔ检验进行统计分析。结果：两种制剂达稳态后Ｃｓｓｍａｘ分别为２６．６±５．６与２６．８±６．２ｍｇ·Ｌ－１，Ｔｍａｘ分别为２．８±０．５与２．７±０．６ｈ，ＡＵＣ０→∞分别为２９８．８±６５．７和２９８．８±７１．１（ｍｇ·Ｌ－１·ｈ），ＦＩ分别是１２３．７％±１９．５％与１２２．３％±２６．０％；以配对ｔ检验与双单侧ｔ检验对上述参数进行统计分析，两种制剂的Ｃｓｓｍａｘ、ＡＵＣ０→∞、Ｔｍａｘ、ＦＩ差异均无显著性（Ｐ＞０．０５）。结论：两者具生物等效性；以芬必得为标准参比制剂，芬尼康相对生物利用度为１０１．７％±１６．８％。     

心痛定片剂与滴丸的人体生物利用度及药代动力学的研究

本文采用高压液相色谱法测定心痛定片剂与滴丸的人体血药浓度。流动相：甲醇（色谱纯）─磷酸盐缓冲液（６０：４０），紫外检测波长２３５ｎｍ，以片剂为标准制剂，滴丸的相对生物利用度为１２２．０％。对片剂与滴丸的ＡＵＣ、Ｃｍａｘ、Ｔｍａｘ作ｔ检验，结果二者之间Ｃｍａｘ、Ｔｍａｘ有显著性差异（Ｐ＜０．０５），ＡＵＣ无显著差异（Ｐ＞０．０５），结果表明滴丸较片剂优良。     

盐酸地尔硫卓与卡马西平在家兔体内的相互作用

本文采用荧光偏振免疫分析（ＦＰＩＡ）法测定卡马西平血药浓度，高效液相色谱分析（ＨＰＬＣ）法测定地尔硫血药浓度，研究在六只家兔体内两药的相互作用。结果表明地尔硫能显著升高卡马西平血药浓度，使其平均峰浓度（Ｃｍａｘ）、药－时曲线下面积（ＡＵＣ）、消除半衰期（Ｔ１／２β）分别增加７０．５％、９０．２％、５７．３％，清除率（ｃｌ）下降５５．４％。上述参数在单、合用药间的差异具有统计学意义（Ｐ＜０．０５）。揭示临床上卡马西平合用地尔硫时，应予酌情减量并加强血药浓度监测。     

多剂量萘普生缓释片及普通片的人体药代动力学和生物利用度研究

８名健康男性受试者连续６ｄ多剂量交叉口服萘普生缓释片和普通片的药代动力学和相对生物利用度研究。结果表明：萘普生缓释片和普通片的Ｔｍａｘ分别为３．５ｈ和１．３ｈ,表明缓释效果明显;经统计分析,萘普生缓释片（５００ｍｇ,ｑｄ）与萘普生普通片（２５０ｍｇ,ｂｉｄ）生物等效;萘普生缓释片的相对生物利用度为９７．０％;２种制剂的其他药代动力学参数如Ｃｍａｘ、Ｃｍｉｎ、ＡＵＣ２４０、ＡＵＣ∞０、ｔ１／２以及波动系数（ＦＩ）等均无显著性差异。     

多剂量萘普生缓释生及普通片的人体药代动力学和生物利 …

８名健康男性受试者连续６ｄ多剂量交叉口服萘普生缓释片和普通片的药代动力学和相对生物利用度研究。结果表明：萘普生缓释片和普通片的Ｔｍａｘ分别为３．５ｈ和１．３ｈ,表明缓释效果明显;经统计分析,萘普生缓释片与萘普生普通片生物等效萘普生缓释片的相对生物利用度为９７．０％;２种制剂的其他药代动力学参数如Ｃｍａｘ、Ｃｍｉｎ、ＡＵＣｏ＾２４、ＡＵＣ０＾∞,ｔ１／２以及波动系数（ＦＩ）等均无显著性差异。     

3－酮－地索高诺酮在家兔体内的药物动力学

以高效液相色谱分析法测定按２ｍｇ·ｋｇ－１剂量给家兔皮下注射３－酮－地索高诺酮后０．２５～２４ｈ的血药浓度，其血药浓度－时间曲线符合二室开放模型，药物动力学方程为Ｃ＝２５７．０７ｅ－０．７１ｔ＋４２．２３ｅ－０．０５ｔ－２９９．３０ｅ－０．９３ｔ主要药物动力学参数：Ｔｋａ０．７８±０．１７ｈ，Ｔα１．２０±０．３０ｈ，Ｔβ１２．０９±４．１８ｈ，ＡＵＣ１３１２．９０±３８７．４５μｇ·ｈ￣（－１）·Ｌ￣（－１），Ｔ＿（ｍａｘ）１．６９±０．３９ｈ，Ｃ（ｍａｘ）＝１２８．２１±５０·７１μｇ·Ｌ￣（－１），Ｖ／Ｆ９．５０±４．３９Ｌ·ｋｇ（－１）。采用平衡透析法测得３－酮－地索高诺酮与兔血浆蛋白的结合率在８１．０９％～８４．６０％之间。     

盐酸洛美沙星颗粒剂血药浓度测定法及其人体生物利用度研究

本文报道利用反相ＨＰＬＣ法测定盐酸洛美沙星的血药浓度，色谱柱为ＹＷＧ－Ｃ１８（５０ｍｍ×４．６ｍｍＩ．Ｄ．１０μｍ），流动相为０．４ｍｏｌ／Ｌ柠檬酸水溶液－甲醇－乙腈（４０：１２：５），四甲基乙二胺调ｐＨ至３．０左右。ＵＶ２８５ｎｍ检测，最低检测浓度为５０ｎｇ／ｍｌ，线性范围为０．１～６μｇ／ｍｌ，方法回收率为９６．４～１００．７％。应用本法对盐酸洛美沙星颗粒剂和胶囊剂进行了人体生物利用度研究，结果表明两种制剂的ＡＵＣ和Ｃｍａｘ均无显著性差异（ｐ＞０．０５），而颗粒剂的Ｔｍａｘ明显快于胶囊剂（ｐ＜０．０２）。     

复方盐酸伪麻黄碱缓释片的研究

应用反相ＨＰＬＣ法测定血药浓度，对复方盐酸伪麻黄碱缓释片的体外溶出及兔灌服一次的药物动力学进行了研究，并与自制普通片进行对照。结果表明缓释片维持体内有效血药浓度的时间较长，其相对生长利用度为１２２．４８％。体内外显著相关。理论值与实测值基本相符。     

Effect of an enteral nutrient formula on sustained-release theophylline absorption

The effect of an enteral nutrient formula (Osmolite) on the absorption of a single oral dose of sustained-release theophylline (Slo-bid) was studied in healthy men. In a randomized, crossover design, subjects received the enteral nutrient diet (2,400 ml/day) or food diet (F) of similar caloric, fat, carbohydrate, protein, and sodium content for 7 days. On day 6 of each diet, volunteers received a single oral dose (600 mg) of sustained-release theophylline (SRT) after fasting or with hourly oral boluses (100 ml) of enteral nutrient formula (ENF). Serial blood samples were collected for 48 h and serum concentrations were analyzed by enzyme multiplied immunoassay. Slight differences (p less than 0.01; paired t test) in Cmax (7.1 +/- 1.2 versus 8.2 +/- 1.3 mg/L) and Tmax (10.7 +/- 2.4 vs. 7.1 +/- 1.1 h) were observed between the ENF and F diets, respectively. However, areas under the curve values were similar (215 +/- 72 versus 211 +/- 70 mg h/L). This study suggests that ENF does not affect the extent of absorption of SRT when administered as a single oral dose.     

不同厂家头孢哌酮含量的比较及其对药动学的影响

本文报道用高效液相色谱法对头孢哌酮国内几个厂家的产品与美国Ｐｆｉｚｅｒ厂的同种药先锋必（Ｃｅｆｏｂｉｄ）的含量进行了比较。国产品含量明显低于进口产品，二者具有显著性差异（ｐ＜０．０５）。同时，通过采取微量耳血测定其血药浓度，对８例住院病人又进行了国内外产品药物动力学的自身对照研究。结果表明：国产品与进口产品相比，峰浓度明显降低（ｐ＜０．０５），药时曲线下面积（ＡＵＣ）明显减少（ｐ＜０．０５），其余药动学参数无明显差异（ｐ＞０．０５）．本研究为临床合理应用该药提供参考数据。     

Plasma theophylline concentrations following the oral administration of microcrystalline theophylline and a new sustained-release theophylline preparation to normal subjects

Summary Plasma theophylline concentrations have been measured in 14 normal subjects following the oral administration of a microcrystalline theophylline preparation (MT) 187.5 mg every 6 h and a sustained-release theophylline preparation (SRT) 375 mg every 12 h for 5 days. During the 5 days, blood samples were drawn before and 2 h after each morning dose with MT, and before and 4.5 h after each morning dose of SRT. On days 1 and 5, more frequent samples were taken during the dose interval. With both preparations, steady-state plasma concentrations were achieved by the third day. The trough levels were significantly higher with SRT than with MT on days 3 and 4, and the levels at 4.5 h after SRT were significantly higher than those measured 2 h after MT on days 3, 4 and 5. Over the terminal 3 days of the study, mean theophylline concentrations with SRT ranged between 11.2 and 15.5 µg/ml at measured trough and peak times, whereas the mean trough levels with MT were always below 10 µg/ml. With adjustment for the dosage differences, the mean ratio of the areas under the plasma concentration/time curves for the final dosage interval for the two formulations (AUC_SRT/AUC_MT) was 1.29±0.56, suggesting that the SRT preparation was well absorbed. The mean steady-state plasma theophylline concentrations (AUC/dose interval) on day 5 were 11.5±4.7 µg/ml with MT and 13.7±5.7 µg/ml with SRT. Nine subjects experienced a total of 35 side-effects whilst taking MT, compared with 10 subjects complaining of 23 side-effects on SRT. These results indicate that, in normal subjects, SRT 375 mg every 12 h exhibited satisfactory sustained-release properties and achieved adequate mean plasma theophylline concentrations during chronic administration. It produced higher plasma levels and a lower incidence of side-effects than the same daily dose of MT.     

盐酸普萘洛尔缓释片与常释片的生物利用度比较研究

目的：通过双交叉试验证明盐酸普萘洛尔缓释片有缓释作用。方法：用HPLC方法,测定血清中普萘洛尔浓度,进行盐酸普萘洛尔缓释片与常释片的生物利用度比较及峰谷浓度波动研究。结果：12位健康男性受试者一次交叉口服缓释片和常释片(均为40 mg)后的C_max分别为62.4±23.3和95.9±12.6 ng.mL^-1,AUC分别为360.2±80.6和383.5±74.2 ng.h.mL^-1,缓释片相对于常释片的相对生物利用度为95%;12位受试者连续服缓释片和常释片后平均稳态浓度分别为42.2±12.2和32.7±7.1 ng.mL^-1,波动度(DF)分别为0.90±0.35和2.09±0.34。结论：两种制剂具生物等效性,且缓释片比常释片有峰谷浓度差异小、血药浓度波动幅度小的特点。     

反式曲马多对映体的药代动力学立体选择性

目的:研究反式曲马多对映体:( + )-反式曲马多和( - )-反式曲马多的人体药代动力学。方法:12 名受试者po 多剂量盐酸反式曲马多缓释片,用高效毛细管电泳法测定人血清中反式曲马多对映体的浓度,配对t-检验比较两对映体的血药浓度和药代动力学参数。结果:血药浓度达稳态后不同时间血清中( + )-反式曲马多的浓度均明显高于( - )-反式曲马多的浓度,两对映体的C_max,C_min ,C_av,AUC_0→∞,T_1/2 等药代动力学参数均有显著性差异。结论:人体对( + )-反式曲马多比对( - )-反式曲马多吸收完全、消除慢,反式曲马多对映体有药代动力学立体选择性。     

In vivo evaluation of the highly soluble oral β-cyclodextrin-Sertraline supramolecular complexes

The aim of the present work was to evaluate the antidepressant like-effect and plasma concentration of Sertraline (SRT) using an inclusion complex (IC) with β-cyclodextrin (βCD) in mice. This supramolecular system was prepared using two different molar ratios at 1:1 and 1:2 SRT:βCD and both were characterized to assess the drug inclusion into the host cavity. Based on the X-ray powder diffraction, Fourier transform infrared spectroscopy and thermal analysis the interaction between host and guest molecules could be suggested. This result indicates that the freeze drying process was efficient to prepare the ICs, when these are compared with the physical mixtures. By comparing the solid state results of 1:1 and 1:2 ICs no significant chemical or structural changes were identified between these systems. However, in vivo experiments indicated that the host-guest ratio was able to modify the SRT activity. Mice treated with both ICs (20mgkg(-1), p.o.) have shown lower immobility time in the tail suspension test in comparison with mice treated with free SRT (20mgkg(-1), p.o.). Mice spontaneous locomotor activity was not affected by any treatment. Higher SRT plasma concentration was determined after 30min of treatment with 1:1 IC in comparison with free SRT, demonstrating the IC greater drug transport efficacy.     

原花青素缓释片对辐射损伤小鼠机体抗应激功能的影响

目的：观察原花青素缓释片对辐射损伤小鼠应激功能的影响。方法：选取150只健康ICR雄性小鼠,随机分为空白对照组、模型组、人参总皂苷阳性药物组、原花青素缓释片低（100mg·kg-1）、高（500mg·kg-1）剂量组。辐照前各组每天分别以0.9%氯化钠溶液和不同剂量药物连续灌胃14d,灌胃至第7天,除空白对照组外,其余各组小鼠均接受6Gy60Co全身性照射1次,照射后继续灌胃7d。通过抗疲劳和耐缺氧实验,观察原花青素缓释片对辐射损伤小鼠抗应激功能的影响。结果：原花青素缓释片低、高剂量组均可以显著延长辐照损伤小鼠负重游泳持续时间,其中,低剂量组与模型组比较,差异有统计学意义（P〈0.05）,阳性对照组、高剂量组与模型组比较,差异均有显著统计学意义（P〈0.01）。高剂量组小鼠耐缺氧时间明显高于模型组（P〈0.01）;低剂量组虽有延长,但与模型组比较差异无统计学意义（P〉0.05）。原花青素缓释片高、低剂量组及阳性对照组均可显著抑制急性缺氧再暴露后丙二醛（MDA）的升高,其中,低剂量组与模型组比较,差异有统计学意义（P〈0.05）,高剂量组与模型组比较差异有显著统计学意义（P〈0.01）。结论：原花青素缓释片对辐射损伤小鼠的机体具有明显增强抵抗力、抗应激功能作用。