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991.
AbstractMass spectrometry plays a pivotal role in drug metabolism studies, which are an integral part of drug discovery and development nowadays. Metabolite identification has become critical to understanding the metabolic fate of drug candidates and to aid lead optimization with improved metabolic stability, toxicology and efficacy profiles. Ever since the introduction of atmospheric ionization techniques in the early 1990s, liquid chromatography coupled with mass spectrometry (LC/MS) has secured a central role as the predominant analytical platform for metabolite identification as LC and MS technologies continually advanced. In this review, we discuss the evolution of both MS technology and its applications over the past 50 years to meet the increasing demand of drug metabolism studies. These advances include ionization sources, mass analyzers, a wide range of MS acquisition strategies and data mining tools that have substantially accelerated the metabolite identification process and changed the overall drug metabolism landscape. Exemplary applications for characterization and identification of both small-molecule xenobiotics and biological macromolecules are described. In addition, this review discusses novel MS technologies and applications, including xenobiotic metabolomics that hold additional promise for advancing drug metabolism research, and offers thoughts on remaining challenges in studying the metabolism and disposition of drugs and other xenobiotics. 相似文献
992.
993.
Corri Black Nara Tagiyeva-Milne Peter Helms Dorothy Moir 《British journal of clinical pharmacology》2015,80(4):844-854
Aims
A systematic review of the literature published in English over 10 years was undertaken in order to describe the use of electronic healthcare data in the identification of potential adverse drug reactions (ADRs) in children.Methods
MEDLINE and EMBASE were searched using MESH headings and text words. Titles, keywords and abstracts were checked for age <18 years, potential ADRs and electronic healthcare data. Information extracted included age, data source, pharmacovigilance method, medicines and ADRs. Studies were quality assessed.Results
From 14 804 titles, 314 had a full text review and 71 were included in the final review. Fifty were published in North America, 10 in Scandinavia. Study size ranged from less than 1000 children to more than 10 million. Sixty per cent of studies used data from one source. Comparative observational studies were most commonly reported (66.2%) with 15% using passive surveillance. Electronic healthcare data set linkage and the quality of the data source were poorly reported. ADRs were classified using the International Classification of Disease (ICD10). Multi-system reactions were most commonly studied, followed by central nervous system and mental and behavioural disorders. Vaccines were most frequently prescribed followed by corticosteroids, general anaesthetics and antidepressants.Conclusions
Routine electronic healthcare records were increasingly reported to be used for pharmacovigilance in children. This growing and important health protection activity could be enhanced by consistent reporting of studies to improve the identification, interpretation and generalizability of the evidence base. 相似文献994.
Aim
The aim of this review was to summarize the prevalence, frequency and comparative value of information on the adverse events of healthcare interventions from user comments and videos in social media.Methods
A systematic review of assessments of the prevalence or type of information on adverse events in social media was undertaken. Sixteen databases and two internet search engines were searched in addition to handsearching, reference checking and contacting experts. The results were sifted independently by two researchers. Data extraction and quality assessment were carried out by one researcher and checked by a second. The quality assessment tool was devised in-house and a narrative synthesis of the results followed.Results
From 3064 records, 51 studies met the inclusion criteria. The studies assessed over 174 social media sites with discussion forums (71%) being the most popular. The overall prevalence of adverse events reports in social media varied from 0.2% to 8% of posts.Twenty-nine studies compared the results from searching social media with using other data sources to identify adverse events. There was general agreement that a higher frequency of adverse events was found in social media and that this was particularly true for ‘symptom’ related and ‘mild’ adverse events.Those adverse events that were under-represented in social media were laboratory-based and serious adverse events.Conclusions
Reports of adverse events are identifiable within social media. However, there is considerable heterogeneity in the frequency and type of events reported, and the reliability or validity of the data has not been thoroughly evaluated. 相似文献995.
Triglycerides (TG) are one of the most common excipients used in oral lipid-based formulations. The chain length of the TG plays an important role in the oral bioavailability of the co-administered drug. Fatty acid (FA) chain-length specificity of porcine pancreatic lipase was studied by means of an in vitro lipolysis model under bio-relevant conditions at pH 6.80. In order to determine the total extent of lipolysis, back-titration experiments at pH 11.50 were performed. Results suggest that there is a specific chain length range (C2–C8) for which pancreatic lipase shows higher activity. This specificity could result from a combination of physicochemical properties of TGs, 2-monoglycerides (2-MGs) and FAs, namely the droplet size of the TGs, the solubility of 2-MGs within mixed micelles, and the relative stability of the FAs as leaving groups in the hydrolysis reaction. During experimentation, it was evident that an optimisation of lipolysis conditions was needed for tighter control over pH levels so as to better mimic in vivo conditions. 1 M NaOH, 3.5 mL/min maximum dosing rate, and 3 μL/min minimum dosing rate were the optimised set of conditions that allowed better pH control, as well as the differentiation of the lipolysis of different lipid loads. 相似文献
996.
To improve solubility of tadalafil (Td), a poorly soluble drug substance (3 μg/ml) belonging to the II class of the Biopharmaceutical Classification System, its six different solid dispersions (1:1, w/w) in the following polymers: HPMC, MC, PVP, PVP-VA, Kollicoat IR and Soluplus were successfully produced by freeze-drying. Scanning electron microscopy showed a morphological structure of solid dispersions typical of lyophilisates. Apparent solubility and intrinsic dissolution rate studies revealed the greatest, a 16-fold, increase in drug solubility (50 μg/ml) and a significant, 20-fold, dissolution rate enhancement for the Td/PVP-VA solid dispersion in comparison with crystalline Td. However, the longest duration of the supersaturation state in water (27 μg/ml) over 24 h was observed for the Td solid dispersion in HPMC. The improved dissolution of Td from Td/PVP-VA was confirmed in the standard dissolution test of capsules filled with solid dispersions. Powder X-ray diffraction and thermal analysis showed the amorphous nature of these binary systems and indicated the existence of dispersion at the molecular level and its supersaturated character, respectively. Nevertheless, as evidenced by film casting, the greatest ability to dissolve Td in polymer was determined for PVP-VA. The crystallization tendency of Td dispersed in Kollicoat IR could be explained by the low Tg (113 °C) of the solid dispersion and the highest difference in Hansen solubility parameters (6.8 MPa0.5) between Td and the polymer, although this relationship was not satisfied for the partially crystalline dispersion in PVP. Similarly, no correlation was found between the strength of hydrogen bonds investigated using infrared spectroscopy and the physical stability of solid dispersions or the level of supersaturation in aqueous solution. 相似文献
997.
Increasing incidence of resistance to azole antifungals has highlighted the importance of the use of alternative therapeutic agents such as nystatin for the treatment of vulvovaginal candidiasis. The aim of the present study was to develop and characterize locally acting, film formulation for the treatment of candidiasis using a derivatized natural polymer. Derivatization of natural polymer was carried out in order to introduce anionic character to an otherwise neutral polymer, so as to enhance its interaction with vaginal mucous membrane along with inheriting the biocompatibility and nonirritant characteristics of its parent polymer. A carboxymethyl derivative of fenugreek gum (CMFG) was prepared, and characterized by DSC, FTIR and X-ray diffraction studies. The derivatized gum was found to possess bioadhesive and film forming properties. A 32 factorial design was employed to formulate vaginal films and a response surface methodological approach was used to study the effect of formulation variables on film properties. Films containing 5% w/v polymer and 2% v/v glycerol exhibited optimum properties in vitro. The optimized drug loaded formulation was able to release 100% drug over a period of 5 h and followed Korsmeyer–Peppas kinetics. It was found to be non-irritant and nontoxic to vaginal mucosa and showed appropriate antifungal properties in vivo. 相似文献
998.
999.
目的:体外诱导近平滑假丝酵母菌( CP)、热带假丝酵母菌( CT)对两性霉素B( AMB)的耐药株,检测其中的耐药基因表达情况。方法 AMB体外构建耐药株,用实时荧光定量PCR法检测耐药基因的表达水平。结果 CP、CT 野生株经体外 AMB 浓度递增法诱导后,形成耐药株最低抑菌浓度( MIC,≥8μg? mL-1);CYP51A、CYP51B、CDR1、CDR2、MDR1及MDR2基因在野生株中低水平表达,在耐药株中表达水平明显升高,差别有统计学意义( P <0.05);CYP51A、CYP51B、CDR1、CDR2、MDR1及MDR2的表达量在CPAMB耐药株中分别是其野生株的136.92,16.33,2.07,14.84,4.07,2.38倍;在CT AMB耐药株中分别是其野生株的8.83,2.98,3.00,2.40,2.30,3.57倍。结论 CP、CT对AMB耐药与CYP51A、CYP51B、CDR1、CDR2、MDR1及MDR2基因过度表达有关。 相似文献
1000.
目的 了解湖南省ICU血标本分离细菌耐药情况.方法 监测2013年度湖南省细菌耐药监测网ICU血标本分离菌株药敏结果,采用CLSI2013年标准判读,用湖南省细菌耐药监测网直报系统在线统计分析药物敏感性.结果 共获得ICU血标本分离细菌1136株,其中革兰阳性菌739株(65.05%);革兰阴性菌397株(34.95%),排名前5位的细菌分别为凝固酶阴性葡萄球菌、大肠埃希菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌.ICU血标本中耐甲氧西林的表皮葡萄球菌、人葡萄球菌、溶血葡萄球菌、金黄色葡萄球菌的检出率分别为75.84%、80.92%、90.29%和36.84%.大肠埃希菌对亚胺培南及美罗培南耐药率分别为1.82%和1.43%,肺炎克雷伯菌对亚胺培南和美罗培南耐药率分别为0和3.03%.铜绿假单胞菌对碳青霉烯类、喹诺酮类、阿米卡星、多黏菌素B、头孢哌酮/舒巴坦的敏感性高于80%.鲍曼不动杆菌对抗菌药物的耐药性普遍高于铜绿假单胞菌,对碳青霉烯类抗菌药物的敏感性均低于50%.结论 ICU血标本分离细菌耐药性较为普遍. 相似文献