葡萄糖酸锌兔体内药物动力学及生物利用度研究

本文介绍用原子吸收分光(?)度法测定葡萄糖酸锌(Zinc Gluconate,ZG)兔体内血清锌浓度,用一室模型分析了ZG 在家兔体内的药动学参数及硫酸锌片剂、ZG 水剂相时于ZG片剂对锌的生物利用度分别为24.9%和62.1%.实验结果表明:ZG 具有口服吸收快,维持时间长,峰浓度高的特点,是一优于硫酸锌的良好补锌剂.     

葡萄糖酸锌健康人体内生物利用度研究

采用原子吸收分光光度法测定葡萄糖酸锌(ZG)在人体内的生物利用度,用一定模型分析了ZG片药动学参数,其相对于硫酸锌片的生物利用度为144.2％。     

葡萄糖酸锌片剂和咀嚼片的生物利用度研究

用原子吸收光谱法测定了葡萄糖酸锌(1)片剂及咀嚼片和对照品硫酸锌片剂的生物利用度。结果表明1两种制剂的生物利用度均高于对照品;并且1咀嚼片的生物利用度又高于1片剂。     

葡萄糖酸锌临床新用途

锌为人体一种必需的微量元素之一，在体内参与多种代谢，与so余种酶的生物活性有关”’。近年来它对人体的重要性已逐渐受到人们的重视。并不断开发研制出许多新的制剂品种。目前临床上应用较多的是硫酸锌和葡萄糖酸锌（ZincGluconate，ZG）。前者为一种无机锌盐，口服吸收效果较差，且有严重的胃肠道方面的不良反应；后者为有机锌盐，生物利用度较好，且胃肠道反应较小，并有增加红细胞产热持续时间的作用D’，儿童口服耐受性良好＊’等优点。有人对ZG在家兔体内的药物动力学及生物利用度进行了研究，证明ZG是一优于硫酸锌的补锌剂’“…     

L—赖氨酸锌片兔体内生物利用度研究

用原子吸收分光光度法测定兔血清锌浓度。结果表明Ｌ－赖氨酸锌片中锌的相对生物利用度明显优于葡萄糖酸锌片和硫酸锌片。     

尼美舒利3种制剂的药代动力学研究

目的:测定尼美舒利在兔体内药物代谢动力学过程,比较片剂、混悬剂、栓剂的药动学参数。方法:用高效液相色谱法测定血浆中尼美舒利浓度,用3P87程序处理血药浓度数据。结果:片剂与混悬剂的药动学参数无显著性差异(P>0.05),栓剂的T_(max)、t1/2ke明显长于片剂和混悬剂,相对于片剂的生物利用度为79.9％,相对于混悬剂的生物利用度为74.5％。     

尼群地平缓释片剂的研究

研究了尼群地平缓释片剂的处方、制备工艺和溶出速率,用GC-MS法测定了12名健康受试者口服自制缓释片(C)、市售国产片剂(A)和进口某公司片剂(B)后的体内血药浓度,体内数据按零级溶出、一级吸收口服单室模型,经计算求得药动学参数。结果表明,A、C两制剂相对于B制剂的生物利用度为31.8％及64.8％。与普通片剂相比,缓释片血浓度曲线较为平坦且下降缓慢。     

硫酸锌控释片的血浆浓度测定与消化道反应观察

原子吸收分光光度法测定表明家犬口服硫酸锌控释片的生物利用度不低于其水溶液。与普通片比较,控释片口服后不引起家犬呕吐。10例志愿者连续服用硫酸锌控释片的试验表明,其血锌浓度平稳。     

尼群地平片剂生物利用度的研究

为提高国产尼群地平片剂的生物利用度,采用球磨混合粉碎法工艺进行处方设计,试制出新处方片剂,与西德Bayer公司片剂进行了体外溶出、体内生物利用度的比较。体内血浆药浓用GC-MS法测定,体内数据按零级溶出、一级吸收口服单室模型,经计算机用Gauss-Newton-Damping法处理求得药动学参数。本文研制的尼群地平新处方片剂生物利用度已超过西德Bayer公司片剂。     

不同厂家尼莫地平片生物利用度比较分析

目的：研究不同厂家尼莫地平片（NIMO）生物利用度的差异。方法 利用HPLC法测定9例人体NIMO血药浓度，对三种国产NIMO片剂的相对生物利用度进行比较。结果 9例健康志愿者自身对照、服用A、B、C三种NIMO片剂120mg后经统计学处理，结果表明，NIMO片剂B与片剂A相比，AUC及Tmax无显著差异（P〉0．05），Cmax有显著差异（0．01〈p〈0．05）。NIMO片剂C与片剂A相比，Tmax无显著差异（P〉0．05），AUC有显著差异（0．01〈P〈0．05），Cmax有极显著差异〈P〈0．01）。NIMO片剂B、C相对于片剂A的相对生物利用度分别为85．23％和52．13％。结论 A厂生产的尼莫地平片（商品名：宝依恬）NIMO具有良好的生物利用度，优于其它厂家。     

Apparent intramolecular acyl migration of zomepirac glucuronide

For the antiinflammatory drug zomepirac (Z), 5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-2 acetic acid, the glucuronic acid conjugate (ZG) is the major metabolite. During analytical development ZG was found to be unstable at physiological pH, leading to four compounds other than Z. ZG and the other fractions were purified from urine by preparative HPLC and the structure of ZG was confirmed by elemental analysis and by NMR and mass spectrometry. Fast atom bombardment mass spectrometry was used to analyze the unstable, underivatized acyl glucuronides. ZG was cleaved by beta-glucuronidase but the other fractions were not. The stability of ZG was determined over a pH range of 1-8; the half-life was 27 min at pH 7.4 and 37 degrees C in water; maximum stability was found at pH 2. Intramolecular acyl migration of the glucuronide is postulated, as four of the isolated fractions formed from ZG yielded a mass-spectral parent ion corresponding to ZG+ H. The importance of sample handling prior to analysis to avoid acyl migration is emphasized.     

异烟肼对利福平的药动学影响

目的：研究异烟肼对利福平的体内药物动力学影响。方法：采用自身对照法2周期两制剂的交叉实验设计，比较了联合给药与单独给药的动力学参数。结果：异烟肼对利福平不存在药物间的不良交互影响。结论：为临床治疗安全有效地使用利福平和异烟肼提供实验依据。     

Role of cAMP in the effects of K+ on the steroidogenesis of zona glomerulosa cells

1. Investigations of the role of cAMP in the stimulation of the steroidogenesis of zona glomerulosa (ZG) cells by increased extracellular K+ concentration are reviewed. 2. Possible reasons for discrepancies in the results of different investigators on whether K+ increases the cAMP content or output of ZG tissue or dispersed cells are discussed. 3. The concentration of cAMP in the incubating media of ZG tissue or cells, rather than their cAMP content, seems to respond more sensitively to stimulation by extracellular K+, as was also found for adrenocorticotropic hormone stimulation of zona fasciculata-reticularis cells. 4. The addition of the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine (IBMX) to incubations with the aim of increasing the sensitivity of the response in cAMP to extracellular K+ in ZG cells may give rise to effects, probably nonspecific, which actually inhibit the measured response. 5. The immediate stimulation in the steroidogenesis of ZG cells with raised extracellular K+ is probably mostly due to the direct effect of increases in cytoplasmic Ca2+ (arising from increases in Ca2+ influx) on mitochondrial processes. However, increases in cAMP may prolong the stimulation of steroidogenesis by increased extracellular K+. This increased cAMP is probably due to stimulation of adenylyl cyclase activity. 6. It has been concluded that the increase in Ca2+ influx output after rises in the extracellular K+ concentration of ZG cells is responsible for most of the increase in cAMP. 7. According to one group of investigators, there is weak stimulation of phospholipase C (PLC) activity after increasing the extracellular K+ concentration of rat ZG cells. 8. If there is such a stimulation of PLC activity, it seems that the action of increased extracellular K+ can potentially involve all known mechanisms for the stimulation of steroidogenesis in endocrine cells. The common primary event is probably the increase in Ca2+ influx. The relative importance of these various potential mechanisms may depend on the particular in vitro conditions used.     

葡萄糖酸锌对顺铂毒性防护作用的实验

小鼠预先给予葡萄糖酸锌后注射顺铂，观察外周血白细胞、肌酐、尿素氮和脂质过氧化物变化。结果表明：葡萄糖酸锌能升高外周血白细胞（Ｐ＜０．０１），降低血清肌酐、尿素氮水平（Ｐ＜０．０１）和荷瘤小鼠肾组织脂质过氧化物水平（Ｐ＜０．０１）。提示：葡萄糖酸锌可望作为顺铂的减毒剂用于肿瘤化疗。     

Macromolecular Carrier Systems for Targeted Drug Delivery: Pharmacokinetic Considerations on Biodistribution

This review article describes the current status and future perspectives of site-specific drug delivery by means of macromolecular carrier systems. Basic aspects and recent advances of targeted delivery of 1) conventional drugs, 2) protein drugs, and 3) gene medicines including antisense oligonucleotides and plasmid DNA, are reviewed from a pharmacokintic perspective. Successful in vivo application of macromolecular carrier systems requires pharmacokinetic considerations at whole body, organ, cellular and subcellular levels. The integration of simultaneous research progress in the multidisciplinary fields such as biochemistry, cell and molecular biology, pharmacology, and pharmacokinetics will accelerate the emergence of marketed drugs with macromolecular carrier systems.     

Mechanistic studies of the toxicity of zinc gluconate in the olfactory neuronal cell line Odora

Zinc is both an essential and potentially toxic metal. It is widely believed that oral zinc supplementation can reduce the effects of the common cold; however, there is strong clinical evidence that intranasal (IN) zinc gluconate (ZG) gel treatment for this purpose causes anosmia, or the loss of the sense of smell, in humans. Using the rat olfactory neuron cell line, Odora, we investigated the molecular mechanism by which zinc exposure exerts its toxic effects on olfactory neurons. Following treatment of Odora cells with 100 and 200 μM ZG for 0–24 h, RNA-seq and in silico analyses revealed up-regulation of pathways associated with zinc metal response, oxidative stress, and ATP production. We observed that Odora cells recovered from zinc-induced oxidative stress, but ATP depletion persisted with longer exposure to ZG. ZG exposure increased levels of NLRP3 and IL-1β protein levels in a time-dependent manner, suggesting that zinc exposure may cause an inflammasome-mediated cell death, pyroptosis, in olfactory neurons.     

布洛芬缓释胶囊生物利用度研究

10名健康志愿者随机交叉口服600mg布洛芬缓释胶囊和芬必得进行药代动力学和相对生物利用度研究。采用高效液相色谱法，测定血清中布洛芬浓度，经3p87药动学计算程序处理，得布洛芬缓释胶囊和芬必得的：AUC分别为147．75±28．78：mg／（L·h）和154．16±26．76mg／（L·h），Tmax分别为4．22±0．73h和4．10±0．83h；Cmax分别为15．97±2．84mg／L和16．76±2．92mg／L，经配对ｔ－检验，两者的AUC、Tmax、Cmax均无显著性差异（P＞0．05）。采用梯形法计算的布洛芬和芬必得的AUC。－t分别为153．53±26．11mg／（L·h）和157．88±23．06mg／（L·h），方差分析和双单侧检验结果表明两者具有生物等效性。布洛芬缓释胶囊相对生物利用度为96．07％。     

Neurotensin stimulates the growth and secretion of rat adrenal zona glomerulosa.

Within 2 days neurotensin (NT) and ACTH administrations markedly enhanced the average volume of zona glomerulosa (ZG) cells and plasma aldosterone concentration (PAC) in intact rats. In dexamethasone-treated rats, both NT and ACTH evoked a clearcut ZG-cell hypertrophy, but only NT was able to raise PAC. In conclusion, our findings indicate that NT is a potent stimulator of the growth and secretion of rat ZG in vivo, and suggest that the mechanism underlying this action of NT does not involve the well-known NT-induced stimulation of ACTH release.     

不同枣粮间作模式物质积累及产量成因分析

在枣粮间作模式下对间作作物的物质积累及产量成因进行对比分析,以玉米品种先育335、高粱品种沈杂5号为试材,分别对其在出苗后45、60、75、90 d和105 d的净光合速率、干物质积累、产量构成因素、株高和茎粗等指标进行了测定与分析。结果表明：在枣粮间作模式下,玉米和高粱分别在ZY4和ZG8模式下粮食产量最高;高粱在各生育时期内的光合速率均高于玉米,在不同生长时期内差异较小,相对玉米可适当密植;在ZY4和ZG8的模式下玉米和高粱干物质积累平均速率高,为高产量的形成奠定物质基础;穗数和粒重受密度影响较大,穗粒数影响较小,ZY4和ZG8模式下枣树、玉米、高粱三者配置模式较好。