SRX pharmacology最新文献

{"title":"The Thermodynamic Dissociation Constants of Clotrimazole, Terbinafine HCL, Acetylsalicylic Acid, Salicylic Acid, and Galanthamine by the Nonlinear Regression of Multiwavelength Spectrophotometric pH-Titration Data","authors":"M. Meloun, Sylva Bordovská, Lubomír Galla","doi":"10.3814/2010/527013","DOIUrl":"https://doi.org/10.3814/2010/527013","url":null,"abstract":"The mixed dissociation constants of five drugs—clotrimazole, terbinafine HCl, acetylsalicylic acid, salicylic acid, and galanthamine—at various ionic strengths I and at temperatures of 25 ° C and 37 ° C were determined with the use of multiwavelength and multivariate treatments of spectral data SPECFIT/32 nonlinear regression analysis and INDICES factor analysis. The factor analysis in the INDICES program predicts the number of components, when the data quality is high and the instrumental error is known. The thermodynamic dissociation constant p K a T was estimated by nonlinear regression of { p K a , I } data at 25 ° C and 37 ° C: for clotrimazole p K a , 1 T = 4.38(1) and 4.16(3); for terbinafine HCl p K a , 1 T = 4.19(3) and 4.12(5); for acetylsalicylic acid p K a , 1 T = 3.49(25) and 3.41(15); for salicylic acid p K a , 1 T = 3.01(1) and 3.00(1) and for galanthamine p K a , 1 T = 8.21(1) and 7.99(2) where in brackets the standard deviation is in the last significant digits. Goodness-of-fit tests for various regression diagnostics enabled the reliability of the parameter estimates found to be proven. Pharma Algorithms predicts p K a being based on the structural formulae of drug compounds.","PeriodicalId":90346,"journal":{"name":"SRX pharmacology","volume":"2010 1","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2010-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70203124","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":"The Utility of Rapid Microbiological and Molecular Techniques in Optimizing Antimicrobial Therapy","authors":"Edward H. Eiland, N. Beyda, Jian Han, W. Lindgren, R. Ward, Thomas M. English, A. Hassoun, Kathi Hathcock","doi":"10.3814/2010/395215","DOIUrl":"https://doi.org/10.3814/2010/395215","url":null,"abstract":"Early treatment of bloodstream infections with appropriate, definitive antimicrobial therapy has proven to reduce mortality, length of hospital stay, and healthcare costs. Culture-based testing methods require up to five days for final pathogen identification and susceptibility reporting, forcing use of broad spectrum empiric therapy. Recently, multiple rapid microbiological and molecular testing methods have been developed that reduce the time to identify the pathogen and susceptibility, allowing optimal antimicrobial therapy to be prescribed earlier. Real-time polymerase chain reaction and gene microarray have been described in literature, yet only peptide nucleic acid fluorescent in-situ hybridization has published data justifying its use based on clinical outcomes and cost savings. Target enriched multiplex polymerase chain reaction was developed to identify both the pathogen and multiple genes associated with resistance from blood within 6 hours and this methodology was studied in our hospital to assess effectiveness at optimizing antimicrobials in staphylococcal bloodstream infections.","PeriodicalId":90346,"journal":{"name":"SRX pharmacology","volume":"2010 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2010-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70202929","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 Progress in the pKa Estimation of Druglike Molecules by the Nonlinear Regression of Multiwavelength Spectrophotometric pH-Titration Data","authors":"M. Meloun, T. Syrový, Jahan B. Ghasemi","doi":"10.3814/2010/481497","DOIUrl":"https://doi.org/10.3814/2010/481497","url":null,"abstract":"Recent developments in the computational diagnostic tools for the p K a estimation of druglike molecules carried out by the nonlinear regression of multiwavelength spectrophotometric pH-titration data are demonstrated on the protonation equilibria of silybin. The factor analysis of spectra predict the correct number of components when the signal-to-error ratio SER is higher than 10. The mixed dissociation constants of the drug silybin at ionic strength I = 0.03 and a temperature of 25 ∘ C were determined using two different programs, SPECFIT32 and SQUAD(84). A proposed experimental and computational strategy for the determination of the dissociation constants is presented. The dissociation constant p K a was estimated by nonlinear regression of the { p K a , I } data at 25 ∘ C with SQUAD (and SPECFIT); that is, p K a 1 = 6.898(0.022) and 6.897(0.002); p K a 2 = 8.666(0.021) and 8.667(0.012); p K a 3 = 9.611(0.010) and 9.611(0.004); p K a 4 = 11.501(0.008) and 11.501(0.007). While great progress has been achieved in terms of the reliability of the protonation model estimation, among the most efficient diagnostics of the nonlinear regression of multiwavelength pH-spectra are the goodness-of-fit test, Cattel's scree plot of the factor analysis, spectra deconvolution, the signal-to-error SER ratio analysis, and other tools of efficient spectra analysis.","PeriodicalId":90346,"journal":{"name":"SRX pharmacology","volume":"2010 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2010-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70203063","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":"Individualization of 5-Fluorouracil in the Treatment of Colorectal Cancer","authors":"L. Alnaim","doi":"10.3814/2010/352491","DOIUrl":"https://doi.org/10.3814/2010/352491","url":null,"abstract":"Chemotherapeutic agents are generally characterized by a large inter-individual pharmacokinetic variability. The balance of efficacy and toxicity is critical and the imbalance can have devastating effects on patients. Standard dosing methods are inadequate in optimizing systemic exposure .Therapeutic drug monitoring (TDM) has the potential to improve the clinical use of chemotherapy agents. TDM has been successfully applied to optimize a few anticancer treatments including carboplatin, methotrexate, and 6-mercaptopurine. 5-Flurouracil (5-FU) is considered the backbone in treatments of advanced CRC. Toxic side effects remain a significant problem despite increased safety of newer regimens. Molecular mechanisms that control DPD-activity are complex and have not been fully elucidated and cannot be used effectively to individualize Fluorouracil dosing as there is no established standard genetic test for DPD deficiency. Current phenotypic methods to measure DPD-activity are cumbersome. A reliable relationship between DPD genotype and 5-FU toxicity phenotype has not been established. Standard dosing of 5FU is by body surface area (BSA). Low correlation exists between exposure and BSA. A better predictor of total exposure is the area under the curve (AUC). Toxicity and efficacy have been correlated to AUC with target of 24-30 (mg.h/l). The therapeutic window is very narrow and difficult to attain by clinical follow-up alone. TDM has been shown effective in adjusting the dose based on AUC.","PeriodicalId":90346,"journal":{"name":"SRX pharmacology","volume":"2010 1","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2010-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70202255","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":"Sustain Released Bupropion in the Treatment of Tricotillomania: Outpatient Follow Up Survey","authors":"P. Dannon, N. Shoenfeld, Oded Rosenberg, M. Kotler","doi":"10.3814/2010/715414","DOIUrl":"https://doi.org/10.3814/2010/715414","url":null,"abstract":"Objectives. Tricotillomania (TTM) is more common than expected. SSRI's are the treatment of choice in TTM. However, response rates are lower with SSRI's. The aim of our study is to explore other pharmacological interventions. Materials and Methods. Nine female TTM patients with SSRI treatment failure were included. Sample was treated with bupropion SR up to 450 mg/day. Results. Six out of nine patients responded well to bupropion SR. Massachusetts General Hospital Hair Pulling Scale (MGH) demonstrated a significant improvement at the twelve week point (f: 32.3, power: 1, lambda: 97.1, P<.0001) and the response rates remained stable at sixteen-month follow up visit. Conclusions. Bupropion SR could be an alternative pharmacological treatment for TTM. Larger samples with double blind placebo controlled design are needed to confirm our preliminary report.","PeriodicalId":90346,"journal":{"name":"SRX pharmacology","volume":"2010 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2010-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70202736","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":"Comparison of Postprandial Responses to a High-Fat Meal in Hypertriglyceridemic Men and Women before and after Treatment with Fenofibrate in the Genetics and Lipid Lowering Drugs and Diet Network (GOLDN) Study.","authors":"Stephen P Glasser,&nbsp;Mary K Wojczynski,&nbsp;A I Oberman,&nbsp;Edmond K Kabagambe,&nbsp;Michael Y Tsai,&nbsp;Jose M Ordovas,&nbsp;Robert J Straka,&nbsp;Donna K Arnett","doi":"10.3814/2010/485146","DOIUrl":"https://doi.org/10.3814/2010/485146","url":null,"abstract":"<p><strong>Context: </strong>The fenofibrate effect on the subclass size distribution of lipoproteins before and after a high-fat challenge is not well studied.</p><p><strong>Objective: </strong>To characterize the baseline and post-prandial response (PPL) to a high-fat challenge following fenofibrate therapy, on changes in LDL, HDL, and VLDL particle subclasses, number, and size in 271 hypertriglyceridemic participants.</p><p><strong>Methods: </strong>Participants from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study who conducted PPL studies both before and after three weeks of fenofibrate (160 mg/d) treatment were analyzed. Particle size distributions were determined using nuclear magnetic resonance imaging, and lipid determinations were measured at fasting (0 hr), 3.5 hours, and 6 hours after ingestion of a standardized high-fat meal. Analyses were stratified by gender. Changes in particle subclass distributions were assessed using repeated measures analysis of variance adjusted for pedigree.</p><p><strong>Results: </strong>Before PPL, fenofibrate in men (adjusted for age, field center, smoking status, diabetes, and weight circumference) lowered fasting and postprandial VLDL primarily due to reductions in postprandial levels of large and medium VLDL particles (9 SE +/-0.7 to 4 +/-0.4 and 78 / -4 to 36 / -3 nmol/L both <i>P</i> < .0001, resp.). Fenofibrate also reduced fasting and postprandial total LDL particles, primarily a result of reduced small LDL particles (1497 = / - 37 to 1088 = / - 36 nmol/L, <i>P</i> < .0001). Directional changes were similar in men and women but the magnitude of change was different for some parameters.</p><p><strong>Conclusion: </strong>Fenofibrate treatment resulted in a lower triglyceride excursion following a high-fat meal. This investigation provides new knowledge of the magnitude and time course of fenofibrate induced attenuation of Lipoprotein subclass size distribution following a postprandial lipid challenge.</p>","PeriodicalId":90346,"journal":{"name":"SRX pharmacology","volume":"2010 ","pages":"485146"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067904/pdf/nihms-499566.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32459666","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}