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11.
Age and gender related changes in stereoselective pharmacokinetics and pharmacodynamics of verapamil and norverapamil. 总被引:2,自引:2,他引:0 下载免费PDF全文
S K Gupta L Atkinson T Tu J A Longstreth 《British journal of clinical pharmacology》1995,40(4):325-331
1. Pharmacokinetics and pharmacodynamics of R- and S-verapamil and R- and S-norverapamil were studied at steady state following administration of 180 mg verapamil delivered by a controlled-release gastrointestinal therapeutic system (COER-verapamil). 2. Of the 30 young (19 to 43 years) and 30 elderly subjects (65 to 80 years) enrolled, approximately half of each age group were women; all subjects were healthy and none were smokers. 3. Mean R- and S-verapamil and R- and S-norverapamil Cmax, Cmin, and AUC values for elderly subjects were 1.2 to 2.2 times greater than those for young subjects; these differences were statistically significant at P < 0.05. Median tmax values for young and elderly subjects were not significantly different for any enantiomer. The mean half-life values of R- and S-verapamil for elderly subjects were approximately 20 h compared with approximately 13 h for young subjects, respectively. The mean half-life values of R- and S-norverapamil for elderly subjects were approximately 31 h and 20 h, respectively, compared with approximately 19 h and 21 h for young subjects, respectively. 4. In both age groups, the mean plasma verapamil concentrations of each enantiomer were higher for women than for men at all time points. 5. Mean arterial pressure (MAP) had a significant correlation to R- (r2 = 0.86) and S-verapamil (r2 = 0.87) concentration values that was not influenced by either gender or age of the patient. Change in PR-interval also had a significant correlation to R- and S-verapamil concentration values. However, the sensitivity of the response to changes in R- and S-verapamil concentration values in elderly subjects was about 1/5 of that in younger subjects. 相似文献
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John Goffin Stefan Baral Dongsheng Tu Dora Nomikos Lesley Seymour 《Clinical cancer research》2005,11(16):5928-5934
PURPOSE: Tumor responses in early-phase trials are used to determine whether new agents warrant further study. Given that spontaneous regressions are observed in melanoma and renal cell carcinoma, this study assessed whether tumor responses, particularly in these two tumor types, predict for future regulatory drug approval. EXPERIMENTAL DESIGN: The literature was reviewed to assess tumor response rates to cytotoxic agents in phase I and II trials in the following solid tumors: melanoma, renal cell carcinoma, non-small-cell lung cancer, breast cancer, ovarian cancer, colorectal cancer, and other solid tumors. Response rates were categorized and the relationship of these categories to the end point of regulatory drug approval was determined. RESULTS: Fifty-eight drugs were assessed in 100 phase I trials, and 46 of these drugs were also studied in 499 phase II trials. Higher overall response rates in both phase I trials (P = 0.03) and phase II trials (P < 0.0001) were predictive of regulatory approval. However, response in melanoma or renal cell carcinoma was not predictive for either phase I or phase II studies. CONCLUSIONS: For cytotoxic agents, although overall objective response rates reliably predict subsequent marketing approval, isolated responses in melanoma and renal cell carcinoma are not predictive. 相似文献
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笔者通过对35例阻塞怀黄疸的CT所见,指出了胆道扩张征象可作为鉴别肝内、阻阻塞性黄疸的可靠指标,再结合临床及CT的初期征象,可更加提高其鉴别诊断准确率。本文对这些指标的可靠性进行重点讨论。提出了该特点是特别胆道管囊肿的重要指征,即后者的胆道扩张为局部性或节段性。本文对良、恶性病变所致的胆道扩张形态亦进行了对照分析,发现二阻之间无明显性差异。 相似文献
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Chih-Hung Chien Tzong-Yang Tu Shu-Feng Chien Angela Chung-I Li Mei-Jan Yang An-Suey Shiao Yi-Fen Wang 《台湾医志》2006,105(10):832-838
BACKGROUND/PURPOSE: In the geriatric population, the reliability of pure-tone threshold (PTT) is sometimes poorer than that in young adults because of various reasons. This study assessed the relationship between Mandarin speech reception thresholds (SRTs) and PTTs in the aged and developed SRT as a measure for corroborating PTT. METHODS: This prospective study enrolled 46 consecutive subjects over 60 years of age. The results of SRT and PTT were collected from one ear randomly selected from each subject. Simple linear and multiple regressions were used to determine the correlation and linear regression coefficients between SRTs and PTTs at various frequencies. RESULTS: In the simple regression analysis, the correlation coefficient was highest at 1000 Hz (r = 0.949) and 500 Hz (r = 0.922), followed by 250 Hz (r = 0.850) and 2000 Hz (r = 0.792). In the multiple regression model with SRT as the dependent variable and PTTs as predictor variables, the resultant multiple correlation coefficient R was 0.967, while R2 was 0.936. In this model, PTTs at the frequencies of 500 Hz and 1000 Hz contributed significantly to the variance in SRTs with p values of 0.029 and < 0.001, respectively. These results demonstrated that the Mandarin SRT is strongly associated with PTTs at the frequencies of 500 Hz and 1000 Hz. CONCLUSION: This study established the agreement between Mandarin SRTs and PTTs in the low tone area of speech frequencies in the geriatric population. In clinical settings, SRT test can be rapidly and easily performed and is relatively inexpensive. It is a vital indicator of the accuracy of PTT measurement. 相似文献
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用基因工程重组的丙肝抗原包被于硝酸纤维素膜,建立了检测丙肝IgG抗体的斑点免疫渗滤法。与ELISA试剂盒进行双盲式同步测定,二法检验结果差异无显著性。渗滤法简便快速,适用于各级医院,有很强的推广价值。 相似文献
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过氧化氢对白色念珠菌DNA破坏的研究 总被引:1,自引:0,他引:1
本文用热变性温度法研究一定浓度 H_2O_2对 C.albicans DNA 破坏作用。结果表明,经6%和10%H_2O_2处理后,C.albicans DNA G c Mol%(分别为28.1±0.82和14.4±1.51)显著低于对照 DNA G C Mol%(85.9±0.62),并推断 H_2O_2可能作用于 C.albicans DNA 碱基以及其间的氢键上;DNA 电泳图谱发现,经3%和6%H_2O_2处理的 C.albicans DNA 电泳带明显不同于对照,提示 H_2O_2更易造成 C.albicans DNA 核苷酸链的降解或断裂.H_2O_2对 C.albicans DNA 的破坏,增强了其杀菌作用。 相似文献