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101.
Shibin Mathew David Tess Woodrow Burchett George Chang Nathaniel Woody Christopher Keefer Christine Orozco Jian Lin Samantha Jordan Shinji Yamazaki Rhys Jones Li Di 《Journal of pharmaceutical sciences》2021,110(4):1799-1823
Volume of distribution at steady state (Vss) is an important pharmacokinetic parameter of a drug candidate. In this study, Vss prediction accuracy was evaluated by using: (1) seven methods for rat with 56 compounds, (2) four methods for human with 1276 compounds, and (3) four in vivo methods and three Kp (partition coefficient) scalar methods from scaling of three preclinical species with 125 compounds. The results showed that the global QSAR models outperformed the PBPK methods. Tissue fraction unbound (fu,t) method with adipose and muscle also provided high Vss prediction accuracy. Overall, the high performing methods for human Vss prediction are the global QSAR models, Øie-Tozer and equivalency methods from scaling of preclinical species, as well as PBPK methods with Kp scalar from preclinical species. Certain input parameter ranges rendered PBPK models inaccurate due to mass balance issues. These were addressed using appropriate theoretical limit checks. Prediction accuracy of tissue Kp were also examined. The fu,t method predicted Kp values more accurately than the PBPK methods for adipose, heart and muscle. All the methods overpredicted brain Kp and underpredicted liver Kp due to transporter effects. Successful Vss prediction involves strategic integration of in silico, in vitro and in vivo approaches. 相似文献
102.
以水溶性α.β.γ.δ—四—(4—三甲铵苯基)卟啉[T-(4-TAP)P]作显色剂,测定了食品中的痕量铜。对实验条件及共存离子的干扰进行了探讨。在乙醇介质及强酸条件下测定时,其选择性及灵敏度均有显著提高。摩尔吸收系数为4.5×10~5 1mol~(-1).cm~(-1)最小检验量为:0.14ng/cm~2,回收率为96.2~106%,变异系数为:0.46~3.6%。操作简便,结果满意。 相似文献
103.
J. W. Wiechers 《Pharmacy World & Science》1989,11(6):185-198
There is currently a high level of interest in using the skin as a route for delivering drugs. The skin, however, provides an efficient barrier against percutaneous absorption of drugs. This barrier function can be ascribed to the macroscopical structure of the stratum corneum, which consists of alternating lipoidal and hydrophylic regions. For this reason, physico-chemical characteristics of the drug, such as partition coefficient and molecular weight, play an important role in determining the facility of percutaneous absorption. Another factor to consider in transdermal drug delivery, is the vehicle in which the drug is formulated as it acts on the release of drug from the formulation. Moreover, vehicles may also interact with human stratum corneum, thereby affecting its barrier function. Surfactants and penetration enhancers are well-known examples of the latter. Subsequently, dosing conditions, such as humidity, temperature and occlusion, also have their impact on the actual input (rate) of drug through human skin. Finally, all bits of information are combined to form a reasonably faithful picture of percutaneous absorption. 相似文献
104.
Alex Avdeef Melissa Strafford Eric Block Michael P. Balogh Walter Chambliss Ikhlas Khan 《European journal of pharmaceutical sciences》2001,14(4):271-280
The assessment of transport properties of 23 drug and natural product molecules was made using the in vitro model based on filter-immobilized artificial membranes (filter-IAM), assembled from phosphatidylcholine in dodecane, in buffer solutions at pH 7.4. Five of the compounds were lactones extracted from the roots of the kava-kava plant. Experiments were designed to test the effects of stirring (0–600 rpm) during assays and the effects of varying the assay times (2–15 h). The highly mobile kava lactones permeated in the order dihydromethisticin (40)>yangonin (37)>kavain (34)>methisticin (32)>desmethoxyyangonin (26), the numbers in parentheses being the measured effective permeabilities in units of 10−6 cm/s. By comparison, commercial drugs ranked: phenazopyridine (35)>testosterone (19)>propranolol (13)>ketoconazole (6.3)>piroxicam (2.2)>caffeine (1.7)>metoprolol (0.8)>terbutaline (0.01). In addition to permeability measurements, membrane retention of compounds was determined. Yangonin, desmethoxyyangonin, ketoconazole, and phenazopyridine were more than 60% retained by the artificial membranes containing phospholipids. Stirring during assay significantly increased the observed permeabilities for highly mobile molecules, but had minimal impact on the poorly permeable molecules. The influence of hydrogen bonding was explored by determining permeabilities using filters coated with dodecane free of phospholipids. In the filter-IAM method, concentrations were determined by microtitre plate UV spectrophotometry and by LC–MS. Higher-throughput was achieved with direct UV by the use of 96-well microtitre plate formats and with LC–MS by the use of cassette dosing (five-in-one). 相似文献
105.
中枢性作用的抗高血压药盐酸可乐定、其透皮吸收制剂称为乐百事膏,用家兔体外剩余法预测其吸收率,贴药后3小时透皮吸收累计约18%、12小时约39.7%、24小时约52.79%,贴药3天后累积吸收约60.7%。由于可乐定用药量小,有效血药浓度极低,须用较精密的分析手段才能准确测出血药浓度,应用体外剩余法可间接了解透皮吸收情况。经实验证明不失为一简单而有效的方法,具有一定的参考价值。 相似文献
106.
目的探讨催化光度法测人头发和天然水中铁含量的测定条件及动力学条件。方法建立Fe(Ⅲ)-H2O2-HSN催化反应体系。以lgA0/Ai值对浓度C作标准曲线图,求出发中Fe(Ⅲ)浓度,并与原子吸收法的测定结果比较,进行相关统计分析。结果本法与原子吸收法所测定结果基本一致。测定范围在0.005~0.035mg/L,检测限为6.3×10-7g/L。结论本法应用于人体发样及天然水中铁的测定,灵敏度高,选择性好,操作简单易行,结果满意。 相似文献
107.
Janne Mannila Kristiina Järvinen Jukka Holappa Laura Matilainen Seppo Auriola Pekka Jarho 《International journal of pharmaceutics》2009
Systemic drug delivery through intraoral membranes may offer a promising administration route for lipophilic peptide drugs. The aim of the present study was to investigate the effect of α-cyclodextrin (α-CD) and a novel chitosan derivative, chitosan N-betainate (CH), on sublingual absorption of a hydrophobic model peptide cyclosporin A (CsA), and the effect of temperature on the complexation of CsA with α-CD. 相似文献
108.
109.
Stéphane Lecleire 《Cahiers de Nutrition et de Diététique》2008,43(1):45-50
Digestion is initiated as soon as the aliments are ingested. Then it is pursued in the digestive tract, by the action of the main enzymes of saliva, gastric juice, pancreatic juice, bile and intestine. Pancreas plays a major role in digestion since it produces the key enzymes of sugars (α-amylase), proteins (trypsin) and lipids (lipase), which change the main aliments in oligosaccharides, oligopeptides and fatty acids. The principal site of digestion is the small intestine. Digestion is initiated by enzymes from pancreatic juice, and finished by the border brush enzymes for proteins and sugars to give amino acids and glucose. Small intestine is also the main site of nutrients absorption, which is facilitated by its 4 meters length. Nutrients absorption is an active phenomenon for glucose and amino acids with a co-transport associated to the sodium. Lipids require a previous solubilization by the biliary acids, which allow a passive diffusion of lipids in the enterocyte after a micelle solubilization. Amino acids and sugars can then pass in the portal vein, whereas fatty acids are changed in triglycerides before their passage in the lymphatic system. 相似文献
110.
刺梨对砷的吸附模型研究 总被引:1,自引:0,他引:1
目的 建立刺梨对重金属砷的吸附模型,探讨其吸附机理.方法 通过检测与刺梨粉达吸附平衡的溶液中砷含量来绘制吸附等温线.结果 吸附量随浓度增加而线性上升,以后逐渐变慢,最后趋于稳定.结论 本模型与实验结果相吻合,初步确定刺梨的解毒机制是以物理吸附为主. 相似文献