枸橼酸梓的急性毒性和药物动力学

应用原子吸收光谱法，以硫酸锌作对照，对枸橼酸锌的急性毒性和在家兔体内的药物动力学进行实验性研究。方法；对家兔做毒性实验和药物动力学研究。结果：此两种药物口服均为开放式一室模型，枸橼酸锌口服毒性低，相对生物利用度为２３６％。结论；枸橼酸锌的毒性较低，对胃肠道的刺激性小，其吸收性好，生物利用度较高。     

氟比洛芬口服混悬剂的兔药物动力学及其生物利用度

目的:研究氟比洛芬口服给药的药物动力学及生物利用度。方法:利用HPLC法测定氟比洛芬的血药浓度,以交叉给药方式分别给予家兔注射剂和口服混悬剂并且对其药物动力学和生物利用度进行研究。结果:氟比洛芬在家兔体内药动学静脉注射符合二室开放模型,口服符合一室开放模型,氟比洛芬口服混悬剂的绝对生物利用度为61.9%。结论:在进行氟比洛芬剂型研究时应注重提高其口服制剂的生物利用度。     

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’“…     

几种诺氟沙星盐的药代动力学及相对生物利用度的比较

诺氟沙星(Norfloxacin, NFLX)是广泛使用的一种喹诺酮类抗菌药物,其抗菌作用强,价格便宜,疗效好,但口服后生物利用度低,因此血浓度不高。作者曾对静注NFLX在家兔体内的药代动力学及口服绝对生物利用度进行了比较,发现NFLX在兔体内的绝对生物利用度仅为8％左右。因此,国内有人将NFLX制成注射剂,供肌内或静脉滴注。本文报道NFLX盐酸盐、醋酸盐及NFLX在家兔体内药代动力学特点及相对生物利用度。 一、给药方法及血样采集     

枸橼酸莫沙必利分散片在健康人体的相对生物利用度

目的 研究两种枸橼酸莫沙必利分散片的生物等效性。方法 22例健康受试者随机交叉、单剂口服试验与参比枸橼酸莫沙必利分散片各10 mg,用HPLc法测定血浆中莫沙必利的药物浓度,计算两制剂的药代动力学参数及相对生物利用度,并进行生物等效性评价。结果 试验与参比枸橼酸莫沙必利分散片AUC0-t分别为117.64 36.88,113.33±41.11μg·h·L-1,Cmax分别为67.27±27.27,62.67±25.68μg·L-1,tmax分别为0.50±O.23,0.75±0.31 h。枸橼酸莫沙比利分散片的相对生物利用度为(107.6±24.7)％。结论两制剂具有生物等效性,但试验药枸橼酸莫沙必利分散片达峰更快。     

α-细辛醚贴剂的家兔相对生物利用度研究

目的：测定α－细辛醚贴剂在家兔体内的相对生物利用度。方法：家兔口服和透皮贴剂交叉试验，分别测定血药浓度和AUC，采用3P97软件中的统计程序计算生物利用度。结果：家兔体内生物利用度试验表明，α－细辛醚贴剂的生物利用度明显高于胶囊剂，贴剂与胶囊剂相对生物利用度为1167．6％。结论：由于α－细辛醚的生物利用度很低，只有2．75－5％，因此，我们制备了α－细辛醚贴剂，实验结果表明，贴剂的生物利用度明显提高，α－细辛醚贴剂这一剂型对α－细辛醚的吸收和 利用都是较为有利的。     

盐酸去氢骆驼蓬碱胶囊兔体内药物动力学及生物利用度研究

目的　研究盐酸去氢骆驼蓬碱胶囊在兔体内的药物动力学及其生物利用度。方法　采用反相高效液相色谱法测定家兔血浆药物浓度。结果　家兔灌胃给盐酸去氢骆驼蓬碱胶囊后血浆药物浓度在 4.73 h左右达峰值(1 .5 2 7mg· L-1) ,消除半衰期为 4.73 h,灌胃给胶囊剂的生物利用度为 1 7.1 4%。结论　家兔灌胃给盐酸去氢骆驼蓬碱吸收迅速 ,但生物利用度较低     

国产麦白霉素正常人生物利用度研究

本文在８例健康成人男性志愿者中进行了进口麦迪霉素与国产麦白霉素生物利用度比较研究，交叉试验设计，口服给药６００ｍ，血清中药物浓度用微生物法测定。结果表明：两种药物从吸收、分布、排泄上都无显著性差异，国产麦白霉素相对生物利用度为１０９．５５％，根据所得药代动力学参数，从生物利用度角度对国产麦白霉素质量进行评价。     

谷氨酸锌溶液剂在兔体内的药物动力学研究

谷氨酸锌溶液剂给兔口服后的药物动力学符合二室模型:k_a=1.25 h~(-1),α=0.64 h~(-1),β=0.37h~(-1),T_(max)=2.85 h,C_(max)=6.43μg/ml。谷氨酸锌溶液的相对生物利用度为66%。谷氨酸锌溶液、硫酸锌溶液和葡萄糖酸锌糖浆药物动力学的比较表明,谷氨酸锌为一种较好的补锌剂。     

葡萄糖酸铜的急性毒性和药代动力学

应用原子吸收光谱法，以硫酸铜作对照，对葡萄糖酸铜的急性毒性和在家兔体内的组织分布及其药代动力学进行了实验研究。结果表明，葡萄糖酸铜口服毒性小，静注毒性较大，但两者的毒性均较硫酸铜为小，而且葡萄糖酸铜吸收后，在家兔体内５种脏器中铜含量均较硫酸铜高。此两种药物口服均为开放式－宝模型，葡萄糖酸铜较硫酸铜达峰时间短，半衰期短，消除速度快，维持时间短，两者在家兔体内代谢过程不一致。     

Inhibition of tetracycline absorption by zinc

Summary The inhibitory effect of zinc on the gastrointestinal absorption of tetracycline has been investigated in 7 healthy volunteers. Zinc (45 mg Zn⁺⁺) was given as a solution of zinc sulphate and as a zinc citrate complex; tetracycline (500 mg) was administered as a commercially available preparation. Serum tetracycline concentrations and the area under the serum tetracycline concentration-time curve (up to 6 h) were significantly reduced when tetracycline was taken with either zinc sulphate or the zinc citrate complex. Although the reduction of absorption seemed more pronounced after zinc sulphate, the difference between the inhibitory effects of the two forms of zinc was not significant. It is concluded that simultaneous administration of zinc and tetracycline may reduce absorption of tetracycline.     

A novel mechanism for the pyruvate protection against zinc-induced cytotoxicity: mediation by the chelating effect of citrate and isocitrate

Intracellular accumulation of free zinc contributes to neuronal death in brain injuries such as ischemia and epilepsy. Pyruvate, a glucose metabolite, has been shown to block zinc neurotoxicity. However, it is largely unknown how pyruvate shows such a selective and remarkable protective effect. In this study, we sought to find a plausible mechanism of pyruvate protection against zinc toxicity. Pyruvate almost completely blocked cortical neuronal death induced by zinc, yet showed no protective effects against death induced by calcium (ionomycin, NMDA) or ferrous iron. Of the TCA cycle intermediates, citrate, isocitrate, and to a lesser extent oxaloacetate, protected against zinc toxicity. We then noted with LC–MS/MS assay that exposure to pyruvate, and to a lesser degree oxaloacetate, increased levels of citrate and isocitrate, which are known zinc chelators. While pyruvate added only during zinc exposure did not reduce zinc toxicity, citrate and isocitrate added only during zinc exposure, as did extracellular zinc chelator CaEDTA, completely blocked it. Furthermore, addition of pyruvate after zinc exposure substantially reduced intracellular zinc levels. Our results suggest that the remarkable protective effect of pyruvate against zinc cytotoxicity may be mediated indirectly by the accumulation of intracellular citrate and isocitrate, which act as intracellular zinc chelators.     

纳米氧化锌安全性评价及化妆品法规管理现状

目的：了解国内外纳米氧化锌安全性评价及化妆品法规管理现状,为我国对纳米原料与纳米化妆品监管提供参考。方法：通过文献研究,总结目前国内外纳米氧化锌的毒理学研究进展及世界主要国家及地区对纳米氧化锌的化妆品法规管理现状。结果：透皮吸收试验发现防晒霜中的纳米氧化锌主要聚集在人体皮肤角质层和毛囊皮脂腺开口处,微量锌可经皮肤吸收进入血液,但不能确定是以氧化锌还是锌离子的形式吸收。体外彗星试验结果显示纳米氧化锌引起人表皮细胞、人鼻粘膜细胞DNA损伤。亚急性经口毒性试验发现纳米氧化锌通过氧化应激介导小鼠肝脏细胞DNA损伤和凋亡。纳米氧化锌对小鼠具有生殖发育毒性。急性吸入毒性试验显示纳米氧化锌导致大鼠肺脏、肝脏组织损伤。亚慢性毒性试验显示纳米氧化锌高剂量组（536.8 mg·kg^-1）SD大鼠出现贫血及轻度到中度胰腺炎,纳米氧化锌的未观察到有害作用水平（NOAEL）为268.4 mg·kg^-1。欧盟、美国、中国台湾已出台了一系列化妆品纳米材料的法规或文件,指导化妆品行业开展纳米材料的安全性评价。结论：化妆品中纳米氧化锌对人体具有潜在安全风险,我国应尽快制定化妆品中纳米原料的相关管理政策。     

Acute toxicity to Daphnia magna of effluents containing Cd,Zn, and a mixture Cd‐Zn,after metal removal by Chlorella vulgaris

Daphnia magna was used as a test organism for assessing the toxicity remaining in simulated effluents containing cadmium, zinc, and a cadmium‐zinc mixture, after these metals were removed with suspended and immobilized Chlorella vulgaris cultures. The percentage of removal was higher (84.7%) for cadmium in the metal mixture with immobilized cultures. The LC₅₀ value was lower for the residual cadmium (single and in the mixture) in the effluent after treatment with suspended cultures. The acute toxicity response observed in D. magna, indicates that zinc has an antagonistic effect on cadmium toxicity. According to the results, the treatment system can modify the Cd acute residual toxicity. © 2000 John Wiley & Sons, Inc. Environ Toxicol 15: 160–164, 2000<     

Different modes of synergistic toxicities between metam/copper (II) and metam/zinc (II) in HepG2 cells: apoptosis vs. necrosis

Both metam sodium and copper/zinc‐containing compounds are widely used as fungicides. They therefore may co‐occur in the biosphere. Despite certain studies of individual toxicity for either metam or copper (II)/zinc (II), their synergistic toxicity has not been examined. In this paper, a remarkable synergistic toxicity was observed in HepG2 cells when metam and copper (II)/zinc (II) at non‐toxic and sub‐toxic levels were combined. Unexpectedly, cell death modes between metam/copper (II) and metam/zinc (II) were different: For metam/copper (II), apoptosis was evident from morphological characteristics including cytoplasm‐chromatin condensation, phosphatidylserine (PS) exposure, SubG₀/G₁ DNA fragmentation, mitochondrial membrane potential decrease, pro/anti‐apoptotic protein activation, and cytochrome c release; for metam/zinc (II), necrosis was evident from organelle swelling and uncontrolled collapse. To our knowledge, this work first not only demonstrates the synergistic toxicities of metam and both copper (II)/zinc (II), but also verifies the different modes of apoptosis/necrosis between metam/copper (II) and metam/zinc (II). © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1964–1973, 2016.     

Cadmium and zinc toxicity to an aquatic insect, Ranatra elongata (Fabr.)

Cadmium chloride and zinc chloride were used to measure their short-term toxicity to an aquatic insect Ranatra elongata (Fabr.). The LC₅₀ values were 0.497, 0.438, 0.355 and 0.288 $\text{mg}\text{l}$ for cadmium chloride and 2.853, 2.456, 1.934 and 1.658 $\text{mg}\text{1}$ for zinc chloride after 24, 48, 72 and 96 h, respectively. Cadmium chloride was found to be more toxic than zinc chloride.     

Comparison of the Effect of Different pH Buffering Techniques on the Toxicity of Copper and Zinc to <Emphasis Type="Italic">Daphnia Magna</Emphasis> and <Emphasis Type="Italic">Pseudokirchneriella Subcapitata</Emphasis>

During the time-course of ecotoxicity tests with algae and chronic (reproductive) toxicity tests with daphnids, in which algae are present as a food source, pH can dramatically increase due to photosynthetic activity. As pH changes can significantly affect metal speciation and thus its bioavailability, it may be necessary to buffer the pH of the exposure medium. One class of buffers (Goods N-subtituted aminosulfonic acids) are increasingly being used in biological and chemical applications, including ecotoxicity testing. However, the potential effect of these buffers on metal toxicity has, so far, scarcely been examined. In this study we investigated if MOPS (3-N morpholino propane sulfonic acid) affected the toxicity of copper and zinc to two standard test organisms: the cladoceran Daphnia magna and the green alga Pseudokirchneriella subcapitata. First, we demonstrate that up to a concentration of 750 mg l^–1 (which proved to be sufficient for pH buffering) MOPS did not affect 21-day net reproduction of D. magna or the 72-h population growth of P. subcapitata. Second, we conducted bioassays in copper and zinc spiked standard media for the pH range 6 – 8. For D. magna the possible effect of 750 mg l^–1 MOPS on acute copper and zinc toxicity was investigated by performing parallel 48-h toxicity tests in NaHCO₃ and MOPS buffered test media. Seventy-two hour growth inhibition assays with P. subcapitata were performed in parallel in MOPS and NaHCO₃ buffered test media and in test media with daily manual pH adjustment with HCl. For daphnids no significant differences in copper and zinc toxicity were observed between MOPS or NaHCO₃ buffered test media. For algae no significant differences in metal toxicity were observed between MOPS and HCl buffered media, but in test media buffered with NaHCO₃ an increased copper and zinc toxicity was observed as a consequence of pH increases during the test. Clearly, the results of this study demonstrate the importance of pH buffering in metal toxicity testing and the suitability of the MOPS buffer for that purpose.     

Pulmonary toxicity of inhaled nanoscale and fine zinc oxide particles: Mass and surface area as an exposure metric

The total surface area is known to be an effective exposure metric for predicting the lung toxicity of low solubility nanoparticles (NPs). However, if NPs are dissolved quickly enough in the lungs, the mass may be correlated with the toxicity. Recent studies have found that the toxicity of zinc oxide (ZnO) NPs was caused by the release of zinc ions. Thus, we hypothesized that mass could be used as an exposure metric for the toxicity of ZnO NPs. Healthy Sprague-Dawley rats were exposed to a low, moderate, or high dose of 35 and 250?nm ZnO particles or filtered air. Bronchoalveolar lavage fluid was collected to determine lung inflammation, injury and oxidative stress. The lung inflammation induced by ZnO particles according to different concentration metrics, including number, mass and surface area, was compared. The mass concentration was significantly correlated with the percentage of neutrophils (R²?=?0.84), number of neutrophils (R²?=?0.84) and total cells (R²?=?0.73). Similarly, surface area concentration was significantly correlated with the percentage of neutrophils (R²?=?0.94), number of neutrophils (R²?=?0.81) and total cells (R²?=?0.76). There was no correlation between the number and lung inflammation. We found that both mass and surface area were effective as metrics for the toxicity of ZnO NPs, although only surface area was previously indicated to be an effective metric. Our results are also consistent with recent study results that ZnO NPs and released zinc ions may play a role mediating the toxicity of NPs.     

Comparative absorption of zinc picolinate, zinc citrate and zinc gluconate in humans

The comparative absorption of zinc after oral administration of three different complexed forms was studied in 15 healthy human volunteers in a double-blind four-period crossover trial. The individuals were randomly divided into four groups. Each group rotated for four week periods through a random sequence of oral supplementation including: zinc picolinate, zinc citrate, and zinc gluconate (equivalent to 50 mg elemental zinc per day) and placebo. Zinc was measured in hair, urine, erythrocyte and serum before and after each period. At the end of four weeks hair, urine and erythrocyte zinc levels rose significantly (p less than 0.005, p less than 0.001, and p less than 0.001) during zinc picolinate administration. There was no significant change in any of these parameters from zinc gluconate, zinc citrate or placebo administration. There was a small, insignificant rise in serum zinc during zinc picolinate, zinc citrate and placebo supplementation. The results of this study suggest that zinc absorption in humans can be improved by complexing zinc with picolinic acid.     

Ferritin and in vivo beryllium toxicity

Beryllium (Be+2), a divalent metal ion, is toxic to both man and animal. Although the molecular basis for its toxicity is unknown, it is well established that micromolar concentrations of beryllium specifically inhibit certain enzymes. Previous in vitro studies have shown that the presence of ferritin, an iron-storage protein, reactivated these enzymes by sequestering beryllium (Price and Joshi, 1984). In the present study we demonstrate in vivo that beryllium and zinc are bound by ferritin in greater amounts than Pb+2, Cu+2, and Cd+2. Beryllium did not induce the synthesis of metallothionein. In animals pretreated with an iron salt (ferric ammonium citrate, 40 mg/kg body wt), liver ferritin was elevated approximately five times and the toxicity of intravenously injected beryllium was significantly attenuated. Excretion and deposition studies suggested that iron salt treatment resulted in a reduction of liver beryllium. Thus the protection against beryllium toxicity by ferric ammonium citrate may be due to increased production of ferritin which binds beryllium and its subsequent elimination in the feces.