SRX pharmacology最新文献

英文中文

The Thermodynamic Dissociation Constants of Clotrimazole, Terbinafine HCL, Acetylsalicylic Acid, Salicylic Acid, and Galanthamine by the Nonlinear Regression of Multiwavelength Spectrophotometric pH-Titration Data 用多波长分光光度法测定氯曲霉唑、盐酸特比萘芬、乙酰水杨酸、水杨酸和加兰他敏的热力学解离常数

SRX pharmacology

Pub Date : 2010-04-19 DOI: 10.3814/2010/527013

M. Meloun, Sylva Bordovská, Lubomír Galla

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.

采用光谱数据SPECFIT/32非线性回归分析和指数因子分析，测定了氯曲霉唑、特比萘芬HCl、乙酰水杨酸、水杨酸和加兰他胺5种药物在不同离子强度I和温度为25℃和37℃时的混合解离常数。在数据质量高且仪器误差已知的情况下，INDICES程序中的因子分析预测组分的数量。在25°C和37°C时，通过{p K a, I}数据的非线性回归估计热力学解离常数p K a T:对于氯曲霉唑p K a, 1 T = 4.38(1)和4.16(3);特比萘芬HCl p K, 1 T = 4.19(3)和4.12(5);对乙酰水杨酸p K a, 1 T = 3.49(25)和3.41(15);对于水杨酸，1 T = 3.01(1)和3.00(1)，对于加兰他明，1 T = 8.21(1)和7.99(2)，括号内的标准差为最后一位有效数字。各种回归诊断的拟合优度检验能够证明所发现的参数估计的可靠性。制药算法根据药物化合物的结构式预测pka。

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引用次数: 7

The Utility of Rapid Microbiological and Molecular Techniques in Optimizing Antimicrobial Therapy 快速微生物学和分子技术在优化抗菌治疗中的应用

SRX pharmacology

Pub Date : 2010-03-28 DOI: 10.3814/2010/395215

Edward H. Eiland, N. Beyda, Jian Han, W. Lindgren, R. Ward, Thomas M. English, A. Hassoun, Kathi Hathcock

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.

血液感染的早期治疗，适当的，明确的抗微生物治疗已被证明可以减少死亡率，住院时间和医疗保健费用。基于培养的检测方法需要长达5天的时间来进行最终病原体鉴定和敏感性报告，迫使使用广谱经验性治疗。最近，多种快速微生物学和分子检测方法已经开发出来，减少了识别病原体和敏感性的时间，从而可以更早地开出最佳的抗菌治疗处方。文献中已经描述了实时聚合酶链反应和基因微阵列，但只有肽核酸荧光原位杂交发表了基于临床结果和成本节约的数据来证明其使用。我们开发了富集靶标的多重聚合酶链反应，用于在6小时内从血液中识别病原体和与耐药相关的多种基因，并在我院研究了该方法，以评估优化葡萄球菌血流感染的抗菌药物的有效性。

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引用次数: 5

Recent Progress in the pKa Estimation of Druglike Molecules by the Nonlinear Regression of Multiwavelength Spectrophotometric pH-Titration Data 多波长分光光度ph滴定数据非线性回归估计类药物分子pKa的研究进展

SRX pharmacology

Pub Date : 2010-03-02 DOI: 10.3814/2010/481497

M. Meloun, T. Syrový, Jahan B. Ghasemi

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.

用多波长分光光度ph滴定数据的非线性回归来估计类药物分子的pka的计算诊断工具的最新进展，在水飞蓟宾的质子化平衡上得到了证明。当信错比SER大于10时，光谱因子分析可以预测正确的组分数。使用SPECFIT32和SQUAD(84)两种不同的程序测定了药物水飞蓟宾在离子强度I = 0.03和温度25°C下的混合解离常数。提出了一种确定解离常数的实验和计算策略。解离常数kp a用SQUAD(和SPECFIT)对25°C时的{kp a, I}数据进行非线性回归估计;即p K a 1 = 6.898(0.022)、6.897(0.002);p K a 2 = 8.666(0.021)和8.667(0.012);p K a 3 = 9.611(0.010)和9.611(0.004);p = 11.501(0.008)和11.501(0.007)。虽然质子化模型估计的可靠性已经取得了很大的进展，但对多波长ph光谱非线性回归最有效的诊断方法是拟合优度检验、因子分析的Cattel屏幕图、光谱反卷积、信错比分析以及其他有效的光谱分析工具。

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引用次数: 3

Individualization of 5-Fluorouracil in the Treatment of Colorectal Cancer 5-氟尿嘧啶个体化治疗大肠癌

SRX pharmacology

Pub Date : 2010-02-23 DOI: 10.3814/2010/352491

L. Alnaim

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.

化疗药物通常具有很大的个体间药代动力学变异性。疗效和毒性的平衡是至关重要的，这种不平衡可能对患者造成毁灭性的影响。标准给药方法在优化全身暴露方面是不够的。治疗性药物监测(TDM)有可能改善化疗药物的临床使用。TDM已成功应用于优化一些抗癌治疗，包括卡铂、甲氨蝶呤和6-巯基嘌呤。5-氟尿嘧啶(5-FU)被认为是晚期结直肠癌治疗的主要药物。尽管新疗法的安全性有所提高，但毒副作用仍然是一个重大问题。控制DPD活性的分子机制是复杂的，尚未完全阐明，不能有效地用于个体化氟尿嘧啶剂量，因为目前还没有DPD缺乏的标准基因检测。目前测量dpd活性的表型方法很繁琐。DPD基因型与5-FU毒性表型之间的可靠关系尚未建立。5FU的标准剂量按体表面积(BSA)计算。暴露与BSA的相关性不高。曲线下面积(AUC)是更好的总暴露预测指标。毒性和药效与AUC相关，靶值为24-30 (mg.h/l)。治疗窗口非常狭窄，仅靠临床随访很难获得。TDM在基于AUC的剂量调节方面已被证明是有效的。

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引用次数: 8

Sustain Released Bupropion in the Treatment of Tricotillomania: Outpatient Follow Up Survey 安非他酮缓释治疗拔毛癖:门诊随访调查

SRX pharmacology

Pub Date : 2010-01-24 DOI: 10.3814/2010/715414

P. Dannon, N. Shoenfeld, Oded Rosenberg, M. Kotler

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.

目标。拔毛癖(TTM)比预期的更常见。SSRI是TTM的治疗选择。然而，SSRI类药物的反应率较低。我们研究的目的是探索其他药物干预措施。材料与方法。纳入9例SSRI治疗失败的女性TTM患者。用盐酸安非他酮450mg /d处理样品。结果。9例患者中有6例对安非他酮有良好的反应。马萨诸塞州总医院拔毛量表(MGH)显示在12周时有显著改善(f: 32.3, power: 1, lambda: 97.1, P< 0.0001)，并且在16个月的随访中有效率保持稳定。结论。安非他酮SR可作为TTM的替代药物治疗。需要双盲安慰剂对照设计的更大样本来证实我们的初步报告。

引用次数: 2

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. 在遗传和降脂药物和饮食网络(GOLDN)研究中，非诺贝特治疗前后高甘油三酯血症男性和女性对高脂肪膳食的餐后反应的比较

SRX pharmacology

Pub Date : 2010-01-01 DOI: 10.3814/2010/485146

Stephen P Glasser, Mary K Wojczynski, A I Oberman, Edmond K Kabagambe, Michael Y Tsai, Jose M Ordovas, Robert J Straka, Donna K Arnett

Context: The fenofibrate effect on the subclass size distribution of lipoproteins before and after a high-fat challenge is not well studied.

Objective: 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.

Methods: 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.

Results: 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 P < .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, P < .0001). Directional changes were similar in men and women but the magnitude of change was different for some parameters.

Conclusion: 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.

背景:非诺贝特对高脂肪攻击前后脂蛋白亚类大小分布的影响尚未得到很好的研究。目的:描述271名高甘油三酯血症患者在非诺贝特治疗后对高脂肪挑战的基线和餐后反应(PPL)， LDL、HDL和VLDL颗粒亚类、数量和大小的变化。方法:对来自降脂药物和饮食网络遗传学(GOLDN)研究的参与者在非诺贝特(160 mg/d)治疗三周前后进行PPL研究进行分析。使用核磁共振成像确定颗粒大小分布，并在空腹(0小时)、3.5小时和摄入标准高脂肪膳食后6小时测量脂质测定。分析按性别分层。颗粒亚类分布的变化是通过重复测量分析来评估的。结果:在PPL之前，男性非诺贝特(根据年龄、场地中心、吸烟状况、糖尿病和体重围度调整)降低了空腹和餐后VLDL，主要是由于餐后大VLDL颗粒和中等VLDL颗粒水平的降低(9 SE +/-0.7至4 +/-0.4和78 / -4至36 / -3 nmol/L, P < 0.0001，分别)。非诺贝特还减少了空腹和餐后总LDL颗粒，主要是由于减少了小LDL颗粒(1497 = / - 37至1088 = / - 36 nmol/L, P < 0.0001)。男性和女性的方向性变化相似，但某些参数的变化幅度不同。结论:非诺贝特治疗导致高脂肪饮食后甘油三酯偏移降低。这项研究提供了非诺贝特诱导的餐后脂质激发后脂蛋白亚类大小分布衰减的幅度和时间过程的新知识。

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