ADMET and DMPK最新文献_第10页

Food effect risk assessment in preformulation stage using material sparing μFLUX methodology. 采用省料μFLUX方法评价制剂预配制阶段的食品效应风险。

IF 2.5

ADMET and DMPK Pub Date : 2022-01-01 DOI: 10.5599/admet.1476

Corinne Jankovsky, Oksana Tsinman, Naveen K Thakral

{"title":"Food effect risk assessment in preformulation stage using material sparing μFLUX methodology.","authors":"Corinne Jankovsky, Oksana Tsinman, Naveen K Thakral","doi":"10.5599/admet.1476","DOIUrl":"https://doi.org/10.5599/admet.1476","url":null,"abstract":"The intake of food and meal type can strongly impact the bioavailability of orally administered drugs and can consequently impact drug efficacy and safety. During the early stages of drug development, only a small amount of drug substance is available, and the solubility difference between fasted state simulated intestinal fluid and fed state simulated intestinal fluid may provide an early indication about the probable food effect. But higher drug solubility in fed state simulated intestinal fluid may not always results in an increased oral absorption. In the present research, we demonstrated using 11 model compounds that in addition to the drug dissolution in biorelevant media, the evaluation of the diffusion flux of a drug in solution, across artificial lipid coated membrane, where only the unbound drug crosses the membrane, is a reliable way to predict the food effect. Although, the combination of dissolution and diffusion flux may not reliably predict the food effect in case of drugs undergoing intestinal metabolism or when transporters are involved in the drug absorption, the technique generally provides good information about the food effect at very early stages of drug development that may help in designing a clinical plan by adjusting the drug dose in the fed state.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"10 4","pages":"299-314"},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10800161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Numerical modeling of the dissolution of drug nanocrystals and its application to industrial product development. 药物纳米晶体溶解的数值模拟及其在工业产品开发中的应用。

IF 2.5

ADMET and DMPK Pub Date : 2022-01-01 DOI: 10.5599/admet.1437

Bastian Bonhoeffer, Andreas Kordikowski, Edgar John, Michael Juhnke

{"title":"Numerical modeling of the dissolution of drug nanocrystals and its application to industrial product development.","authors":"Bastian Bonhoeffer, Andreas Kordikowski, Edgar John, Michael Juhnke","doi":"10.5599/admet.1437","DOIUrl":"https://doi.org/10.5599/admet.1437","url":null,"abstract":"The apparent solubility of drug nanocrystals in equilibrium was experimentally determined for a drug-stabilizer system with different particle size distributions. True supersaturation was identified for ultrafine drug nanocrystals with an almost 2-fold increase compared to the thermodynamic solubility of related coarse drug crystals, highlighting their enabling potential to enhance bioavailability. The experimental results were applied to investigate in silico the associated dissolution behavior in a closed system by numerical modeling according to the Ostwald-Freundlich and Noyes-Whitney / Nernst-Brunner equations. Calculated results were found to be in agreement with the experimental results only when the entire particle size distribution of drug nanocrystals was considered. In silico dissolution, studies were conducted to simulate the complex interplay between drug nanocrystals, dissolution conditions and resulting temporal progression during dissolution up to the equilibrium state. Calculations were performed for selected in vivo and in vitro scenarios considering different drug nanocrystal particle size distributions, drug amount, dissolution media and volume. The achieved results demonstrated the importance of ultrafine drug nanocrystals for potential bioavailability improvement and the functional applicability of the modeling approach to investigate their dissolution behavior for configurable formulation variables in product development in terms of in vivo and in vitro relevant conditions.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"10 4","pages":"253-287"},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10800155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ten years for PhysChem Forum-Japan (PCF-J). 物理计划论坛-日本(PCF-J)十年。

IF 2.5

ADMET and DMPK Pub Date : 2022-01-01 DOI: 10.5599/admet.1452

Takashi Mano

引用次数: 0

Development of fiber optic in vitro release testing method for dexamethasone release from the oil solutions. 地塞米松油溶液释放度的光纤体外释放测试方法的建立。

IF 2.5

ADMET and DMPK Pub Date : 2022-01-01 DOI: 10.5599/admet.1465

Filip Kozlina, Ivan Meštrović, Viktor Novak, Nikola Marjanović, Biserka Cetina-Čižmek

{"title":"Development of fiber optic in vitro release testing method for dexamethasone release from the oil solutions.","authors":"Filip Kozlina, Ivan Meštrović, Viktor Novak, Nikola Marjanović, Biserka Cetina-Čižmek","doi":"10.5599/admet.1465","DOIUrl":"https://doi.org/10.5599/admet.1465","url":null,"abstract":"For many parenteral drugs, there is still no standardized method for in vitro release (IVR) testing available. This article presents the development of a new IVR method for oil solutions using a dialysis membrane and USP II apparatus coupled to a fiber optic UV-Vis spectrometer. Experiments were performed using dexamethasone formulations containing castor oil as a solvent with the addition of cosolvents, 20 % (v/v) of isopropanol or Capryol® 90. Based on solubility testing results, castor oil was chosen as the best solvent amongst other vegetable oils, while a significant increase in solubility was obtained by adding either of the two cosolvents. Partitioning experiments were performed to ensure these formulations could achieve prolonged drug release. IVR testing was performed with model formulations and critical test parameters were varied in order to examine the method’s sensitivity. The developed method was sensitive to temperature and stirring rate, while coupling the USP II apparatus with a fiber optic UV-Vis spectrometer enabled complete automation. Moreover, due to the interference of excipients on fiber optic detection of dexamethasone during the release testing, derivative spectroscopy was successfully introduced for the elimination of the interference. The developed IVR method described herein could be useful in preformulation investigations and the early development of novel formulations.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"10 4","pages":"315-329"},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10800158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of silymarin–selenium nanoparticle conjugate and examination of its biological activity in vitro 水飞蓟素-硒纳米颗粒缀合物的合成及其体外生物活性研究

IF 2.5

ADMET and DMPK Pub Date : 2021-11-14 DOI: 10.5599/admet.1023

S. Staroverov, S. Kozlov, A. Fomin, K. Gabalov, Vitaliy Khanadeev, D. Soldatov, I. Domnitsky, L. Dykman, S. Akchurin, O. Guliy

引用次数: 6

Bacteriocin-mediated inhibition of some common pathogens by wild and mutant Lactobacillus species and in vitro amplification of bacteriocin encoding genes 细菌素介导的野生和突变乳杆菌对一些常见病原体的抑制作用及细菌素编码基因的体外扩增

IF 2.5

ADMET and DMPK Pub Date : 2021-11-14 DOI: 10.5599/admet.1053

A. Ahsan, B. Mazhar, Muhammad Kamran Khan, Madiha Mustafa, M. Hammad, N. Ali

{"title":"Bacteriocin-mediated inhibition of some common pathogens by wild and mutant Lactobacillus species and in vitro amplification of bacteriocin encoding genes","authors":"A. Ahsan, B. Mazhar, Muhammad Kamran Khan, Madiha Mustafa, M. Hammad, N. Ali","doi":"10.5599/admet.1053","DOIUrl":"https://doi.org/10.5599/admet.1053","url":null,"abstract":"Lactobacilli are the most common probiotics used in food and other industries because of their capability of producing bacteriocins. Bacteriocins are compounds that are used to kill pathogenic microorganisms. As most bacteria have become resistant to synthetic antibacterial tools, the importance of using probiotics as antibacterial agents has increased. This work was done to check the bacteriocin effect on some common pathogens and the influence of mutation on the bacteriocin activity of Lactobacilli was also investigated. Four strains were isolated, identified from meat and pickles samples via culturing methods, staining, biochemical tests, and ribotyping. Preliminary tests, including Gram staining and catalase test, were done for the confirmation of Lactobacillus species. All strains were gram-positive and catalase-negative. Antibacterial activity was checked against Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus thuringiensis, Escherichia coli, and Salmonella enteritis via agar well diffusion method. The mutations were done using ethidium bromide and the influence of wild and mutants were also checked. Interestingly, mutants developed more virulence than wild ones. It was also observed that they all were sensitive to pepsin. Protein estimation was done via Bradford method. Ribotyping of GCU-W-PS1 revealed 99 % homology with Lactobacillus plantarum and GCU-W-MS1 to Lactobacillus curvatus (99 % homology). Curvacin A, sakacin P, and plantaricin A genes were also amplified using specific primers. Gene sequence showed the presence of curvacin A gene in GCU-W-MS1. It was concluded that lactic acid bacteria could be used as antibacterial tools against common pathogens.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"49 1","pages":"75 - 87"},"PeriodicalIF":2.5,"publicationDate":"2021-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84920366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Newly discovered Staphylococcus aureus serine hydrolase probe and drug targets 新发现的金黄色葡萄球菌丝氨酸水解酶探针及药物靶点

IF 2.5

ADMET and DMPK Pub Date : 2021-10-28 DOI: 10.5599/admet.1137

M. Fellner

引用次数: 2

Drug-like Properties and Fraction Lipophilicity Index as a combined metric 药物样性质和分数亲脂性指数作为联合度量

IF 2.5

ADMET and DMPK Pub Date : 2021-10-08 DOI: 10.5599/admet.1022

A. Tsantili-Kakoulidou, V. Demopoulos

{"title":"Drug-like Properties and Fraction Lipophilicity Index as a combined metric","authors":"A. Tsantili-Kakoulidou, V. Demopoulos","doi":"10.5599/admet.1022","DOIUrl":"https://doi.org/10.5599/admet.1022","url":null,"abstract":"Fraction Lipophicity Index (FLI) has been developed as a composite drug-like metric combining log P and log D in a weighted manner. In the present study, an extended data set confirmed the previously established drug-like FLI range 0-8 using two calculation systems for log P/log D assessment, the freeware MedChem Designer and ClogP. The dataset was split into two classes according to the percentage of fraction absorbed (%FA) - class 1 including drugs with high to medium absorption levels and class 2 including poorly absorbed drugs. The FLI and FLI-C (ClogP based FLI) drug-like range covers 92 % and 91 % of class 1 drugs, respectively. Using MlogP, a narrower drug-like FLI-M range 0-7 was established, covering 91 % of class 1 drugs. The dependence of the degree of ionization to intrinsic lipophilicity within the FLI (FLI-C, FLI-M) drug-like range as well as the inter-relation between the other Ro5 properties (Mw, HD, HA) was explored to define drug-like / non-drug-like combinations as a safer alternative to single properties for drug candidates’ prioritization. In this sense, we propose a combined metric of Mw and the number of polar atoms (Mw/NO) to account for both size and polarity. Setting the value 50 as cutoff, a distinct differentiation between class 1 and class 2 drugs was obtained with Mw/NO>50 for more than 70 % of class 1 drugs, while the opposite was observed for class 2 drugs.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"71 1","pages":"177 - 190"},"PeriodicalIF":2.5,"publicationDate":"2021-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86246549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Investigating antimicrobial features and drug interactions of sedoanalgesics in intensive care unit: an experimental study 研究重症监护病房中sedo镇痛药的抗菌特性和药物相互作用:一项实验研究

IF 2.5

ADMET and DMPK Pub Date : 2021-09-06 DOI: 10.5599/admet.1042

Ozge Unlu, Emre Bingul, S. Kesi̇ci̇, M. Demirci

{"title":"Investigating antimicrobial features and drug interactions of sedoanalgesics in intensive care unit: an experimental study","authors":"Ozge Unlu, Emre Bingul, S. Kesi̇ci̇, M. Demirci","doi":"10.5599/admet.1042","DOIUrl":"https://doi.org/10.5599/admet.1042","url":null,"abstract":"Study Objective Aim of this study was to evaluate antimicrobial effects and interaction between analgesic combinations of fentanyl citrate, dexmedetomidine hydrochloride and tramadol hydrochloride on Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa and Candida albicans which are some of the most common nosocomial infection related microorganisms. Design In vitro prospective study. Setting University Clinical Microbiology Laboratory. Measurements In order to evaluate in vitro antimicrobial effects and interaction between analgesic combinations, tramadol hydrochloride, fentanyl citrate and dexmedetomidin were used against S. aureus ATCC 29213, K. pneumoniae, E. coli ATCC 25922, P. aeruginosa ATCC 27853 and C. albicans ATCC 10231 standard strains by microdilution method. Main Results According to microdilution assays tramadol has shown the most efficient antimicrobial activity also it has been observed that 10 μg/ml concentrated dexmedetomidine has antimicrobial effects on S. aureus, K. pneumoniae and P. aeruginosa. Fentanyl has displayed evident inhibitory potency on the pathogens except for Klebsiella pneumoniae, nevertheless our predefined minimum concentration inhibited growth by 9.5 %. Fentanyl and dexmedetomidine together exhibited more antimicrobial effect on P. aeruginosa and E. coli growth. Additionally, when the three drugs examined together, microbial inhibition occurred more than expected on E. coli again and also on C. albicans growth. Conclusions Our results revealed the antimicrobial properties and synergy with the different combinations of fentanyl, dexmedetomidine and tramadol against the most common nosocomial infection agents in the ICU. This is the first study in the literature looking into the microbial “interactions” of opioids and sedative drugs but more research is needed in order to define clinico-laboratory correlation.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"57 1","pages":"219 - 226"},"PeriodicalIF":2.5,"publicationDate":"2021-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81509092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Are we ready to design oral PROTACs®? 我们准备好设计口服PROTACs®了吗?

IF 2.5

ADMET and DMPK Pub Date : 2021-08-31 DOI: 10.5599/admet.1037

Diego García Jiménez, M. Rossi Sebastiano, G. Caron, G. Ermondi

{"title":"Are we ready to design oral PROTACs®?","authors":"Diego García Jiménez, M. Rossi Sebastiano, G. Caron, G. Ermondi","doi":"10.5599/admet.1037","DOIUrl":"https://doi.org/10.5599/admet.1037","url":null,"abstract":"PROTACs® are expected to strongly impact the future of drug discovery. Therefore, in this work we firstly performed a statistical study to highlight the distribution of E3 ligases and POIs collected in PROTAC-DB, the main online database focused on degraders. Moreover, since the emerging technology of protein degradation deals with large and complex chemical structures, the second part of the paper focuses on how to set up a property-based design strategy to obtain oral degraders. For this purpose, we calculated a pool of seven previously ad hoc selected 2D descriptors for the 2258 publicly available degraders in PROTAC-DB (average values: MW= 972.9 Da, nC= 49.5, NAR= 4.5, PHI= 17.3, nHDon= 4.5, nHAcc= 17.7 and TPSA= 240 Å2) and compared them to a dataset of 50 bRo5 orally approved drugs. Then, a chemical space based on nC, PHI and TPSA was built and subregions with optimal permeability and bioavailability were identified. Bioavailable degraders (ARV-110 and ARV-471) tend to be closer to the Ro5 region, using mainly semi-rigid linkers. Permeable degraders, on the other hand, are placed in an average central region of the chemical space but chameleonicity could allow them to be located closer to the two Arvinas compounds.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"16 1","pages":"243 - 254"},"PeriodicalIF":2.5,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90062833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10