ADMET and DMPK最新文献

{"title":"Levothyroxine sodium loaded dissolving microneedle arrays for transdermal delivery.","authors":"Riyam F Ghazi,&nbsp;Mohammed H Al-Mayahy","doi":"10.5599/admet.1317","DOIUrl":"https://doi.org/10.5599/admet.1317","url":null,"abstract":"<p><p>Levothyroxine (LT-4) sodium has shown variable bioavailability following oral administration. This can be assigned to the significant influence of gastrointestinal conditions, food and drugs administered concomitantly on the rate and extent of absorption from the gastrointestinal tract. Thus, the aim of this research study was to establish an efficient transdermal delivery system of LT-4 sodium via the application of hyaluronic acid dissolving microneedles. Microneedles-based drug delivery system consists of sharp-tip needles that puncture the top layers of the skin in a minimally invasive manner to create physical channels through which therapeutic molecules can easily diffuse into/across the skin. Hyaluronic acid polymer at different ratios (5-60 %) was used to prepare microneedle arrays (100 needles per array) using a micromoulding technique. Characterisation tests were carried out to select the optimum formulation. F11 formula containing 50% w/v hyaluronic acid and 1% v/v Tween 80 formula showed an appropriate needle shape with dimensions of 432 ± 6.4 μm in height and a tip diameter of 9.8 ± 1.3 μm. The microneedle arrays demonstrated a suitable mechanical strength after applying a force of 32 N per array and an excellent insertion ability both in Parafilm M® and human skin. The in vivo dissolution of microneedles was started rapidly within 5 minutes following the insertion in the skin and completed at 1 hour. Ex vivo permeation study using human skin has shown a significant improvement in LT-4 sodium delivery across the skin compared to control preparations (drug solution and microneedle free film). The microneedle array F11 has significantly (P ≤ 0.05) increased LT-4 sodium permeation through the skin (cumulative permeated amount of 32 ± 2 μg/cm²) in comparison to the control solution (cumulative permeated amount of 0.7 ± 0.07 μg/cm²) and the microneedle free film (cumulative permeated amount of 0.1 ± 0.02 μg/cm²) over 7 hours. The findings from the irritation test revealed that mild erythema was produced from the application of microneedle arrays which disappeared within 24 hours. Accordingly, dissolving hyaluronic acid microneedles could be a feasible and effective approach to delivering LT-4 sodium transdermally without causing significant skin damage.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"10 3","pages":"213-230"},"PeriodicalIF":2.5,"publicationDate":"2022-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33466455","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}

{"title":"Silver(I) complexes with phenolic Schiff bases: Synthesis, antibacterial evaluation and interaction with biomolecules.","authors":"Natalia Loginova,&nbsp;Maxim Gvozdev,&nbsp;Nikolai Osipovich,&nbsp;Alina Khodosovskaya,&nbsp;Tatiana Koval'chuk-Rabchinskaya,&nbsp;Galina Ksendzova,&nbsp;Dzmitry Kotsikau,&nbsp;Anatoly Evtushenkov","doi":"10.5599/admet.1167","DOIUrl":"https://doi.org/10.5599/admet.1167","url":null,"abstract":"<p><p>Novel Ag(I) complexes (<b>2a</b>-<b>2c</b>) with phenolic Schiff bases were synthesized using 4,6-di-tert-butyl-3-(((5-mercapto-1,3,4-thiadiazol-2-yl)imino)methyl)benzene-1,2-diol (<b>1a</b>), 4,6-di-tert-butyl-3-(((4-mercaptophenyl)imino)methyl)benzene-1,2-diol (<b>1b</b>), and 4,6-di-tert-butyl-3-(((3-mercaptophenyl)imino)methyl)benzene-1,2-diol (<b>1c</b>). They were examined by elemental analysis, FT-IR, UV-Vis, ¹H-NMR spectroscopy, XRD, cyclic voltammetry, conductivity measurements, and biological methods. The complexes are characterized by distorted geometry of the coordination cores AgN₂S₂ (<b>2c</b>), AgNS (<b>2b</b>) and AgS₂ (<b>2a</b>). These stable complexes were not typified by the intramolecular redox reaction in organic solvents resulting in the formation of silver nanoparticles (AgNPs). Antibacterial activity of <b>1a</b>-<b>1c</b> and <b>2a</b>-<b>2c</b> was evaluated in comparison with AgNPs and commonly used antibiotics. All the complexes were more active than the ligands against the bacteria tested (14), but they were less active than AgNPs and commonly used antibiotics. Both <b>1a</b>-<b>1c</b> and their complexes <b>2a</b>-<b>2c</b> exhibited the capability for the bovine heart Fe(III)-Cyt c reduction. The ligands <b>1b</b> and <b>1c</b> were characterized by the highest reduction rate among the compounds under study, and they showed a higher reducing ability (determined by cyclic voltammetry) as compared with that of their Ag(I) complexes <b>2b</b> and <b>2c</b>.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"10 3","pages":"197-212"},"PeriodicalIF":2.5,"publicationDate":"2022-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33466456","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}

{"title":"Pharmacokinetics of ceftriaxone-tazobactam (8:1) combination in healthy and <i>Escherichia coli</i> induced diarrhoeic birds.","authors":"U C Mithin,&nbsp;Rinku Buragohain,&nbsp;Pradip K Das,&nbsp;Tapan K Mandal,&nbsp;Rabindra N Hansda,&nbsp;Siddhartha N Joardar,&nbsp;Indranil Samanta,&nbsp;Tapas K Sar","doi":"10.5599/admet.1170","DOIUrl":"https://doi.org/10.5599/admet.1170","url":null,"abstract":"<p><p>Antibiotic-resistant <i>Escherichia coli</i> infection of poultry causes significant economic losses. Extended spectrum β lactamases (ESBL) producing <i>E. coli</i> was inoculated in a broiler, Rhode Island Red and Haringhata Black birds orally at 56×10⁸ c.f.u. mL^-1 for induction of diarrhoea. Pharmacokinetics of ceftriaxone-tazobactam combination (8:1) was studied following a single intramuscular injection at 28.125 mg kg^-1 and the combination was administered twice daily to treat such infection. Plasma concentration of both ceftriaxone persisted up to 8 h in experimental birds and maintained an approximate ratio of 8:1 with tazobactam for a period of 2 h, 0.25 h and 0.75 h, respectively in a broiler, Rhode Island Red and Haringhata Black birds. The <i>K</i> _el was significantly lower in all experimental birds compared to healthy birds. Efficacy study was conducted in diarrhoeic birds by administration of ceftriaxone-tazobactam combination at 28.125 mg kg^-1 body weight twice daily intramuscularly for three days which caused an increase in specific antibody titre in the broiler on 5^th day and in Rhode Island Red birds 10^th day. However, Haringhata black birds were inherently showed more resistance towards the infection. The combination of ceftriaxone and tazobactam in the ratio of 8:1 can be an effective treatment to combat ESBL producing <i>E. coli</i> infections.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"10 3","pages":"180-196"},"PeriodicalIF":2.5,"publicationDate":"2022-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33466457","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}

{"title":"Recent advances and challenges in antibacterial drug development","authors":"V. Gigante, Hatim F Sati, P. Beyer","doi":"10.5599/admet.1271","DOIUrl":"https://doi.org/10.5599/admet.1271","url":null,"abstract":"The abstract is not provided being a short comunication / featured article.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"16 1","pages":"147 - 151"},"PeriodicalIF":2.5,"publicationDate":"2022-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82026695","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}

{"title":"Recent advances in nanoparticles as antibacterial agent.","authors":"Murat Ozdal,&nbsp;Sumeyra Gurkok","doi":"10.5599/admet.1172","DOIUrl":"https://doi.org/10.5599/admet.1172","url":null,"abstract":"<p><p>Recently, the rapid increase in antibiotic-resistant pathogens has caused serious health problems. Researchers are searching for alternative antimicrobial substances to control or prevent infections caused by pathogens. Different strategies are used to develop effective antibacterial agents, and in this respect, nanoparticles are undoubtedly promising materials. Nanoparticles act by bypassing drug resistance mechanisms in bacteria and inhibiting biofilm formation or other important processes related to their virulence potential. Nanoparticles can penetrate the cell wall and membrane of bacteria and act by disrupting important molecular mechanisms. In combination with appropriate antibiotics, NPs may show synergy and help prevent the developing global bacterial resistance crisis. Furthermore, due to characteristics such as enhanced biocompatibility and biodegradability, polymer-based nanoparticles enable the development of a wide range of medical products. Antibacterial applications of nanoparticles range from antimicrobial synthetic textiles to biomedical and surgical devices when nanoparticles are embedded/loaded/coated into different materials. In this review, the antibacterial mechanisms of nanoparticles and their potential for use in the medical field are discussed.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"10 2","pages":"115-129"},"PeriodicalIF":2.5,"publicationDate":"2022-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419610","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}

{"title":"Realistic and critical review of the state of systemic antimicrobial peptides","authors":"Guangshun Wang, A. Mechesso","doi":"10.5599/admet.1215","DOIUrl":"https://doi.org/10.5599/admet.1215","url":null,"abstract":"Antimicrobial peptide research remains active not only because of the growing antibiotic resistance problem but also our desire to understand the role of innate immune peptides in host defense. While numerous peptides are currently under active development for topical use, this article highlights peptides with systemic efficacy. The scaffolds of these peptides range from linear to cyclic forms. The neutropenic mouse model is well established to illustrate antimicrobial efficacy from direct killing. The majority of tests, however, are conducted using normal mice so that both direct antimicrobial and immune regulatory effects can be characterized. These systemic examples underscore the possibility of adding new candidates to the list of the existing peptide antibiotics to more effectively combat antibiotic-resistant bacteria, fungi, and parasites.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"56 1","pages":"91 - 105"},"PeriodicalIF":2.5,"publicationDate":"2022-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88823986","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}

{"title":"Therapeutic potential of interferon-gamma in tuberculosis","authors":"S. Berns, J. Isakova, Polina Pekhtereva","doi":"10.5599/admet.1078","DOIUrl":"https://doi.org/10.5599/admet.1078","url":null,"abstract":"Tuberculosis is one of the critical health problems worldwide. The search for ways to improve the results of tuberculosis treatment and overcome drug resistance lies in understanding the pathogenesis of the development of the infectious process. The interferon system, particularly the role of interferon-gamma, has been identified as the main link in the immune response in tuberculosis. The clinical efficacy of interferon-gamma has been studied and evaluated in clinical trials since the end of the last century. There was obtained evidence of the clinical efficacy of interferon-gamma as part of complex therapy. Recent experimental data make it possible to consider interferon-gamma as a promising therapeutic option for the treatment of multidrug-resistant tuberculosis as part of complex therapy worthy of further studies.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"23 1","pages":"63 - 73"},"PeriodicalIF":2.5,"publicationDate":"2022-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76162804","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}

{"title":"Synthesis and diverse biological activity profile of triethylammonium isatin-3-hydrazones","authors":"A. Bogdanov, O. Tsivileva, A. Voloshina, A. Lyubina, S. Amerhanova, Ekaterina Burtceva, S. Bukharov, Alexander V. Samorodov, V. Pavlov","doi":"10.5599/admet.1179","DOIUrl":"https://doi.org/10.5599/admet.1179","url":null,"abstract":"A series of biorelevant triethylammonium isatin hydrazones containing various substituents in the aromatic fragment have been synthesized. Their structure and composition were confirmed by NMR- and IR-spectroscopies, mass-spectrometry and elemental analysis. It was found that some representatives show activity against Staphylococcus aureus and Bacillus cereus higher or at the level of norfloxacin, including methicillin-resistant Staphylococcus aureus strains. The study also showed low hemo- and cytotoxicity (Chang Liver) and high antiaggregatory and anticoagulant activity of these compounds. The high potential of new ammonium isatin-3-acylhydrazones in the search for antimicrobial activity against phytopathogens of bacterial and fungal nature has been shown for the first time.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"26 1","pages":"163 - 179"},"PeriodicalIF":2.5,"publicationDate":"2022-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88276481","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}

{"title":"Bioanalysis of aminoglycosides using high-performance liquid chromatography","authors":"S. Amponsah, Joseph A. Boadu, Daniel K. Dwamena, K. F. Opuni","doi":"10.5599/admet.1183","DOIUrl":"https://doi.org/10.5599/admet.1183","url":null,"abstract":"Aminoglycosides are broad-spectrum antibiotics used in the treatment of gram-negative bacterial infections. Due to their nephrotoxic and ototoxic potential (narrow therapeutic index), the use of aminoglycoside for clinical indications requires monitoring. The objective of this review was to identify relevant literature reporting liquid chromatographic methods for the bioanalysis of aminoglycosides in both preclinical and clinical settings/experiments. Data on liquid chromatographic methods were collected from articles in an online academic database (PubMed, Science Direct, Scopus, and Google Scholar). All 71 articles published from 1977 to 2020 were included in the review. Reversed-phase liquid chromatography was the most used method for the bioanalysis of aminoglycosides. Fluorescence or ultraviolet detection methods were mostly used from 1977 to 2002 (51 articles), while mass spectrometry was predominantly used as a detector from 2003 to 2020 (15 articles). Sixty-seven articles reported calibration ranges, which varied significantly for the various drugs assayed: some in the range of 0.1-0.5 ng/mL and others 1250-200000 ng/mL. Also, 61 articles reported R2 values (0.964-1.0) for almost all analytes under consideration. Sixty-three articles reported percent recoveries mostly between 61.0 % to 114.0 %, with only two articles reporting recoveries of 4.9 % and 36 %. Out of the 71 reviewed articles, 56 reported intermediate precision values ranging between 0.331 % to 19.76 %, which is within the acceptable limit of 20 %. This review will serve as a guide for research and/or routine clinical monitoring of aminoglycosides in biological matrices.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"56 1","pages":"27 - 62"},"PeriodicalIF":2.5,"publicationDate":"2022-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87641306","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}

{"title":"Impact of host factors on susceptibility to antifungal agents","authors":"B. Plotkin, M. Konaklieva","doi":"10.5599/admet.1164","DOIUrl":"https://doi.org/10.5599/admet.1164","url":null,"abstract":"An obstacle to drug development, particularly in this era of multiple drug resistance, is the under-appreciation for the role the host environment plays in microbial response to drugs. With the rise in fungal infection and drug resistance, particularly in individuals with co-morbidities, the influence serum and its components have on antimicrobial susceptibility requires assessment. This study examined the impact of physiologically relevant glucose and insulin levels in the presence and absence of 50 % human plasma on MICs for clinical isolates of Candida lusitaniae, Candida parapsilosis, Candida albicans, Candida tropicalis, Candida glabrata, Candida krusei and Cryptococcus neoformans. The addition of insulin or glucose at physiologic levels in RPMI medium alone altered the MIC in either a positive or negative fashion, depending on the organisms and drug tested, with C. glabrata most significantly altered with a 40, >32- and 46-fold increase in MIC for amphotericin B, itraconazole and miconazole, respectively. The addition of candida-antibody negative plasma also affected MIC, with the addition of glucose and insulin having a tandem effect on MIC. These findings indicate that phenotypic resistance of Candida and Cryptococcus can vary depending on the presence of insulin with glucose and plasma. This modulation of resistance may help explain treatment failures in the diabetic population and facilitate the development of stable drug-resistant strains. Furthermore, these findings indicate the need for a precision approach in the choice of drug treatment and drug development.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"106 1","pages":"153 - 162"},"PeriodicalIF":2.5,"publicationDate":"2022-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74345043","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}