共查询到20条相似文献,搜索用时 109 毫秒
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Ⅰ期临床试验之目的是研究人体对药物的耐受程度,并通过药物代谢动力学研究,了解药物在人体内的吸收、分布、代谢和消除的规律,为制定给药方案提供依据.Ⅰ期临床试验必须全过程高度重视受试者的安全.因此,加强试验中健康受试者的管理是非常必要的.主要包括受试者的招募、培训、筛选、食宿、用药等环节的管理. 相似文献
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我国是肺结核病高发病率的国家之一.因此有必要在筛选期开展受试者肺结核筛查,并在临床试验长周期随访中做好受试者及研究人员结核防控也尤为重要.本文根据专病特点和Ⅰ期临床实践情况进行经验分享,供行业人员参考. 相似文献
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袁丽 《临床合理用药杂志》2024,(8):158-161
目的 分析国内Ⅰ期临床试验受试者权益相关研究的发展情况,为后续研究提供参考。方法 通过计算机检索中国知网和万方医学网数据库1996—2021年国内发表的关于Ⅰ期临床试验受试者权益相关研究的文献,通过文献管理软件和可视化分析软件,分析发文量、载文期刊、机构及地区分布、相关作者、关键词、获基金支持情况、研究方向等。结果 符合纳入标准的文献266篇,发文量逐年增加,涉及期刊97种;《中国新药杂志》载文量25篇,位居第1位;发文量最多的机构是四川大学华西医院,发文量为7篇;发文量排名前5位的地区为北京、江苏、湖北、广东、四川;出现频次较高的词分别是受试者(28次)和依从性(9次)、管理(9次)、健康受试者(7次)、受试者管理(6次)等;涉及研究基金资助11种,对研究资助最多的地区是北京。结论 通过对国内Ⅰ期临床试验研究受试者权益相关文献的分析,可了解该研究领域现状和存在的不足,为后续研究、合作、交流提供参考价值。 相似文献
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P Bernardi L Bastagli M Cavazza C Minelli C Ventura F Fontana A Danieli G Bartolini V Tommasi M Orlandi 《International journal of clinical pharmacology research》1987,7(6):455-461
The mechanism of muzolimine (3-amino-1-[3,4-dichloro-alpha-methyl-benzyl]-2 pyrazolin-5-one) action is still not completely defined. The identified site of action is the Henle loop, similarly to furosemide which acts also by mediating renal prostaglandin synthesis. The aim of the present study was to evaluate the early effects of muzolimine (30 mg per os) on renal function and prostaglandin urinary excretion in healthy controls and hypertensive subjects. Urinary flow reached the peak values by the third hour after the drug and a diuretic effect not directly dependent on glomerular filtration was observed, especially in hypertensive patients. In these cases the diuresis increased also due to a low glomerular filtration rate and tubular phenomena were more evident than in controls: an increasing Na+ tubular excretion and a parallel decreasing % Na+ reabsorption. Blood pressure was not significantly influenced by muzolimine in healthy subjects, while it returned to normal values in the hypertensive group. A cyclooxigenase inhibitor, lysine acetylsalicylate (1 g i.m.) administered 10 minutes after muzolimine, was not able to modify the parameters under consideration. Therefore a mediation by prostaglandins on the diuretic and antihypertensive effects of the drug under study may probably be excluded. 相似文献
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G. Lemm J. Küppers R. Frey W. Wingender J. Kuhlmann 《European journal of clinical pharmacology》1998,54(4):287-294
Objective: The quantitative measurement of urinary marker proteins may improve the sensitivity of monitoring renal function in healthy male subjects in phase I studies. Little is known about the variability of physiological proteinuria in young, healthy male subjects. Thus, the biological and analytical variability of three marker proteins, i.e. albumin, α1-microglobulin and N-acetyl-β-d-glucosaminidase (NAG), were investigated in this population. Methods: Seven young, healthy male subjects participated in a prospective two-way cross-over study, and 139 in a retrospective study. Albumin and α1-microglobulin were determined by immunological methods (radial immunodiffusion and/or kinetic nephelometry), and NAG by enzyme activity in a colorimetric assay. Results: The inter-assay precision of NAG, albumin and α1-microglobulin is good (<15%) if automated kinetic nephelometry is applied for albumin and α1-microglobulin determination, but less impressive (<25%) with radial immunodiffusion. The highest frequency of detectable proteinuria and highest creatinine-adjusted protein levels are found in the second morning urine voided after a night's rest. The intra-individual biological variability of NAG excretion from day to day is low (CV: 15–25%), irrespective of outpatient or inpatient settings. By contrast, albumin and α1-microglobulin excretion can differ by a factor of 2–3 from day to day, and higher levels are predominantly found in outpatient settings. The reference ranges for young, healthy male subjects are generally lower than published in cross-sectional studies in the total healthy population. Conclusion: These findings and established reference ranges for young, healthy male subjects may assist in the evaluation of proteinuria in clinical pharmacological phase I trials. 相似文献
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R. Schüppel B. Boos G. Bühler M. Lataster T. Peters 《European journal of clinical pharmacology》1996,51(3-4):215-219
Objective: Participants in a phase I study were interviewed in order to establish the incidence and variability of subjective symptoms
and changes in quality of life during phase I trials. Methods: The healthy subjects were randomized to receive a single dose of either 0.5 mg digoxin or an equivalent amount of each of
four digitaloid mixtures every 14 days. The trial involved five 24-h monitoring periods. The duration of the study was 57
days. Wellbeing, subjective symptoms and quality of life were measured before, during and after the trial using the Freiburg
Symptoms List (FSL), Wellbeing Scales (WBS), and Life Satisfaction Questionnaire (LSQ).
Results: Eight healthy subjects (25 years) were enrolled in the study. Their subjective symptoms were below the reference values
for healthy subjects for each test but above the theoretical minimum and maximum values for total wellbeing, indicating that
healthy subjects – not just patients – display subjective symptoms and impairment of wellbeing to a greater or lesser extent
prior to a clinical trial. In terms of the total study population, comparison of the questionnaire scores before, during and
after the study disclosed no significant changes in wellbeing or quality of life. However, some participants displayed marked
intraindividual fluctuation.
Conclusions: A careful exploration of the baseline symptoms is necessary even in healthy subjects to avoid observation bias. The symptom
course differs greatly from individual to individual; therefore in a phase I study only group scores of wellbeing should be
used to assess the possible effects of trial-related factors. A setting like the one used in our study does not impair the
quality of life of healthy subjects and as such can be regarded as a fairly neutral means of measuring wellbeing.
Received: 18 March 1996/Accepted in revised form: 5 July 1996 相似文献
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目的 探讨如何提高生物等效性试验健康受试者筛选期的工作效率.方法 试验甲给予受试者根据各个检查项目等待人数自由分流的筛选方法;试验乙给予对部分检查项目进行先后顺序限定,并要求研究者在发现受试者某项检查结果异常后,应及时终止其继续参加其他检查的筛选方法.比较2个试验中受试者在某项检查不合格时合并有其他项目检查的情况.结果... 相似文献
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Hormonal effects of MPV-2213ad, a new selective aromatase inhibitor, in healthy male subjects. A phase I study 总被引:1,自引:1,他引:1 下载免费PDF全文
Outi Ahokoski Kerttu Irjala Risto Huupponen Kaija Halonen Eeva Salminen & Harry Scheinin 《British journal of clinical pharmacology》1998,45(2):141-146
Aims A novel non-steroidal competitive inhibitor of the aromatase enzyme, MPV-2213ad, was entered into an open dose-escalation study. The objective of this study was to investigate the tolerability and efficiency of this new compound with assessment of the hormonal effects after study drug administration.
Methods MPV-2213ad was given to 39 healthy male volunteers. Single increasing oral doses of 0.003, 0.03, 0.3, 3, 9, 30 and 100 mg were given to three subjects at each dose level, after which ten subjects received the 300 mg dose and eight subjects the highest 600 mg dose of MPV-2213ad.
Results Serum oestradiol levels were suppressed by 58–65% when MPV-2213ad was given at doses between 0.3 and 30 mg. A reduction in serum oestradiol levels by 83% from baseline was achieved with the 300 mg dose. No additional decrease was seen with the highest dose. The suppression lasted longer with higher doses of MPV-2213ad. After the 300 and 600 mg doses serum oestradiol returned to baseline within 4 days. Marked increases in serum concentrations of testosterone, androstenedione, 17-OH-progesterone, LH and FSH were also observed at doses between 100 and 600 mg of MPV-2213ad. The drug was well-tolerated and the adverse events were mild or moderate including hot flushes, mild vertigo, nausea, acne and gastrointestinal discomfort.
Conclusions MPV-2213ad has a potent, dose-dependent inhibitory effect on serum oestradiol. It was selective for the aromatase enzyme with no signs of adreno-cortical suppression or haematological or biochemical toxicity. 相似文献
Methods MPV-2213ad was given to 39 healthy male volunteers. Single increasing oral doses of 0.003, 0.03, 0.3, 3, 9, 30 and 100 mg were given to three subjects at each dose level, after which ten subjects received the 300 mg dose and eight subjects the highest 600 mg dose of MPV-2213ad.
Results Serum oestradiol levels were suppressed by 58–65% when MPV-2213ad was given at doses between 0.3 and 30 mg. A reduction in serum oestradiol levels by 83% from baseline was achieved with the 300 mg dose. No additional decrease was seen with the highest dose. The suppression lasted longer with higher doses of MPV-2213ad. After the 300 and 600 mg doses serum oestradiol returned to baseline within 4 days. Marked increases in serum concentrations of testosterone, androstenedione, 17-OH-progesterone, LH and FSH were also observed at doses between 100 and 600 mg of MPV-2213ad. The drug was well-tolerated and the adverse events were mild or moderate including hot flushes, mild vertigo, nausea, acne and gastrointestinal discomfort.
Conclusions MPV-2213ad has a potent, dose-dependent inhibitory effect on serum oestradiol. It was selective for the aromatase enzyme with no signs of adreno-cortical suppression or haematological or biochemical toxicity. 相似文献
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Sheng Feng Ji Jiang Pei Hu Jian-yan Zhang Tao Liu Qian Zhao Bi-lu Li 《Acta pharmacologica Sinica》2012,33(11):1353-1358
Aim:
To investigate the pharmacokinetics, pharmacodynamics, and safety of higenamine, an active ingredient of Aconite root, in healthy Chinese volunteers.Methods:
Ten subjects received continuous, intravenous infusion of higenamine at gradually escalating doses from 0.5 to 4.0 μg·kg−1·min−1, each dose was given for 3 min. Blood and urine samples were collected at designated time points to measure the concentrations of higenamine. Pharmacodynamics was assessed by measuring the subject''s heart rate. A nonlinear mixed-effect modeling approach, using the software Phoenix NLME, was used to model the plasma concentration-time profiles and heart rate.Results:
Peak concentrations (Cmax) of higenamine ranged from 15.1 to 44.0 ng/mL. The half-life of higenamine was 0.133 h (range, 0.107–0.166 h), while the area under concentration-time curve (AUC), extrapolated to infinity, was 5.39 ng·h·mL−1 (range, 3.2-6.8 ng·h·mL−1). The volume of distribution (V) was 48 L (range, 30.8–80.6 L). The total clearance (CL) was 249 L/h (range, 199-336 L/h). Within 8 h, 9.3% (range, 4.6%–12.4%) of higenamine was recovered in the urine. The pharmacokinetics of higenamine was successfully described using a two-compartment model with nonlinear clearance. In the pharmacodynamic model, heart rates were related to the plasma drug concentrations using a simple direct effect model with baseline. The E0, Emax, and EC50 were 68 bpm, 73 bpm and 8.1 μg/L, respectively.Conclusion:
Higenamine has desirable pharmacokinetic and pharmacodynamic characteristics. The results provide important information for future clinical studies on higenamine. 相似文献19.
目的讨论选择正确的药靶在新药研发过程中的重要性。方法作者以近年来发表的21篇中外文献为依据,以细胞膜G蛋白偶合受体、生长因子受体、细胞膜离子通道蛋白、细胞核受体为例,介绍药靶的筛选、确认以及在此基础上筛选出的代表性药物。结果与结论随着分子遗传学、功能基因组学、蛋白质组学和生物信息学的快速进展,越来越多的功能清楚的生物学分子正在被发现,这其中的某些基因及其产物由于被证明与疾病发生和发展相关而成为分子药靶,选择正确的药靶在新药研发过程中具有重要作用。 相似文献