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排序方式: 共有379条查询结果,搜索用时 15 毫秒
1.
Stanislas Grassin‐Delyle Michaela Semeraro Frantz Foissac Naim Bouazza Haleema Shakur‐Still Ian Roberts Jean‐Marc Treluyer Saïk Urien 《Fundamental & clinical pharmacology》2019,33(6):670-678
Tranexamic acid (TXA) is an antifibrinolytic drug that reduces surgical blood loss and death due to bleeding after trauma and post‐partum haemorrhage. One key issue for treatment success is early administration. While usually given intravenously, oral and intramuscular use would be useful in specific circumstances. Therefore, an understanding of TXA pharmacokinetics when given via different routes is valuable. The aim of this study was to perform an individual participant data meta‐analysis of pharmacokinetic studies with TXA given to healthy volunteers via different routes. We searched the following databases: PubMed, Web of Science, Wiley Online Library, Elsevier Science Direct and J‐STAGE. Individual subject data were extracted when available, otherwise arithmetic means were used. A population pharmacokinetic model was developed using nonlinear mixed effect modelling. Seven studies were included in the analysis with data from 10 patients for the IV route, six patients for the IM route and 114 patients for the oral route. The pharmacokinetics was ascribed to a two‐compartment model, and the main covariate was allometrically scaled bodyweight. Oral and IM bioavailabilities were 46 and 105%, respectively. For a 70 kg bodyweight, the population estimates were 7.6 L/h for clearance, 17.9 L for the volume of the central compartment, 2.5 L/h for the diffusional clearance and 16.6 L for the peripheral volume of distribution. Larger well‐designed studies are needed to describe the pharmacokinetics of TXA when given IM or as an oral solution before these can be recommended as alternatives to IV. 相似文献
2.
The aim of laboratory screening in Phase I is to exclude subjects with subclinical illness, who might be at increased risk in the study, and who might also adversely influence interpretation of the results. A new method for laboratory screening, based on Bayesian probability theory, is proposed, which consists of: 1. Drawing up a list of diseases to be excluded. 2. Defining for each disease, the maximum acceptable risk that an included subject could be affected by it. 3. Identifying one test for each disease. 4. Using a contingency table to calculate the specificity of the test and integrating the estimated prevalence of the disease from epidemiological data. 5. Applying the percentage obtained by the calculation of specificity to the previously determined distribution of values in the volunteer population to identify the threshold value for inclusion. Use of this deductive method in screening volunteers for Phase I trials affords increased security of selection, while reducing the number of non-pertinent exclusions because of laboratory findings. 相似文献
3.
A. Fjellestad-Paulsen L. d’Agay-Abensour P. Höglund J.-C. Rambaud 《European journal of clinical pharmacology》1996,50(6):491-495
Objective: The bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP), with and without an enzyme inhibitor,
was studied in six healthy, male volunteers aged 19–34 years, followed for 8 h after each drug administration.
Methods:
For i.v. administration the subjects received 4 μg dDAVP. For intestinal administration 500 μg dDAVP was administered directly,
in two separate sessions, in the first part of the duodenum via a triple-lumen channel tube. In one session a solution of
isotonic polyethylene glycol (PEG) was given as a continuous enteral perfusion. In the other session a solution of PEG and
aprotinin was administered enterally at the constant rate of 5 ml⋅min−1 for 4 h. Plasma dDAVP was measured using a specific, sensitive radioimmunoassay and intestinal juice was collected for measurement
of lipase, chymotrypsin and pH every 30 min for 5 h.
Results:
The intestinal chymotrypsin activity was decreased after perfusion of aprotinin while the lipase activity was not modified.
After i.v. administration, the half-life of elimination of dDAVP was 1.56 h and plasma clearance 1.24 ml⋅min⋅kg−1. The mean bioavailability after duodenal administration of dDAVP + aprotinin was 0.46% compared with 0.09% after duodenal
administration of dDAVP alone. The bioavailability of dDAVP after direct duodenal administration of an aqueous solution was
similar to that after swallowing a tablet in a previous study and increased 5 times when given together with a perfusion of
an enzyme inhibitor.
Received: 27 October 1995/Accepted in revised form: 26 February 1996 相似文献
4.
243例健康人血红细胞悬浮液射频介电特性的研究 总被引:8,自引:0,他引:8
本文应用同轴传输线反射法建立的细胞悬浮液介电测量系统,测量了243例健康人(男120,女123名)血红细胞悬浮液在1~500MHz频率范围的介电常数和电导率。结果表明不同性别和不同血型之间的红细胞悬浮液的介电参数无显著差异。将19~80岁之间的受试者按10岁年龄间隔分成六个组,探讨年龄差别对介电参数的影响;发现50岁左右是人红细胞介电参数有显著差异的临界年龄,49岁后三个高年龄组的介电参数显著地低于49岁前的三个低年龄组的数值(P<0.05)。本文的结果证明年龄对人血红细胞的介电参数有明确的影响。 相似文献
5.
Faaij RA Srivastava N van Griensven JM Schoemaker RC Kluft C Burggraaf J Cohen AF 《European journal of clinical pharmacology》1999,54(12):929-935
Objective: Pentosan polysulphate sodium (PPS), a heparin-like drug, is supposed to be orally applicable. The objective of the present
study was to assess the oral bioavailability of PPS. However, since specific assays for PPS do not exist, this was done by
using primary and secondary effect parameters.
Methods: The study was carried out using a three-way randomized crossover design with 18 healthy young male volunteers. The subjects
received three treatments: PPS i.v. (50 mg), PPS orally (1500 mg) and placebo (orally). Blood sampling was done for activated
partial thromboplastin time (APTT), anti-Xa activity, hepatic triglyceride lipase, lipoprotein lipase, tissue plasminogen
activator (t-PA) activity, fibrin plate lysis, total triglyceride, total cholesterol, HDL and LDL.
Results: Intravenously administered PPS significantly increased APTT, anti-Xa activity, hepatic triglyceride lipase and lipoprotein
lipase compared with placebo in a magnitude comparable to other i.v. heparin-like compounds. Orally administered PPS did not
significantly influence any of the parameters when compared with placebo. Point estimates for the oral bioavailability of
PPS were in the range of 0% with small confidence intervals (CIs).
Conclusion: The oral bioavailability of PPS is negligible in young healthy males.
Received: 8 June 1998 / Accepted in revised form: 19 October 1998 相似文献
6.
7.
目的探讨高校志愿者居家养老护理服务的参与意愿,以有效发挥高校志愿者作为居家养老护理服务主体的积极作用。方法自编高校志愿者居家养老护理参与意愿调查问卷,对470名高校志愿者进行调查。结果在生活护理中,高校志愿者对打扫卫生(77.4%)和上街购物(74.5%)的参与意愿较强;在医疗保健护理项目中,对于健康知识讲解(78.9%)的参与意愿最强;精神慰藉服务项目中,对读书读报(88.1%)和聊天解闷(82.6%)的参与意愿最强。为他人作贡献(67.0%)是高校志愿者参加居家养老护理最主要的原因。结论高校志愿者对居家养老护理的不同方面存在不同的参与意愿,应结合其参与意愿,将高校志愿者资源合理地整合到居家养老护理服务主体中,以有效促进居家养老护理事业的发展。 相似文献
8.
钱雪飞 《南通大学学报(哲学社会科学版)》2015,(4)
本文基于南通市“巾帼挽霞行动”社工服务项目的实践探索,通过对社区志愿者、社团志愿者及高校学生志愿者持续参与志愿服务状况的比较分析,认为志愿服务由社团来承担具有诸多的优越性。社团应逐步成为持续志愿服务的承担主体。社团的志愿服务化以及志愿者的社团化应该成为持续志愿服务管理的努力方向。 相似文献
9.
Yan-xia Lu Qing-hong Su Ke-hua Wu Yu-peng Ren Liang Li Tian-yan Zhou Wei Lu 《Acta pharmacologica Sinica》2015,36(2):281-288
Aim:
To develop a population pharmacokinetic (PopPK) model of tacrolimus in healthy Chinese volunteers and liver transplant recipients for investigating the difference between the populations, and for potential individualized medication.Methods:
A set of 1100 sparse trough concentration data points from 112 orthotopic liver transplant recipients, as well as 851 dense data points from 40 healthy volunteers receiving a single dose of tacrolimus (2 mg, po) were collected. PopPK model of tacrolimus was constructed using the program NONMEM. Related covariates such as age, hepatic and renal functions that were potentially associated with tacrolimus disposition were evaluated. The final model was validated using bootstrapping and a visual predictive check.Results:
A two-compartment model of tacrolimus could best describe the data from the two populations. The final model including two covariates, population (liver transplant recipients or volunteers) and serum ALT (alanine aminotransferase) level, was verified and adequately described the pharmacokinetic characteristics of tacrolimus. The estimates of V2/F, Q/F and V3/F were 22.7 L, 76.3 L/h and 916 L, respectively. The estimated CL/F in the volunteers and liver transplant recipients was 32.8 and 18.4 L/h, respectively. Serum ALT level was inversely related to CL/F, whereas age did not influence CL/F. Thus, the elderly (≥65 years) and adult (<65 years) groups in the liver transplant recipients showed no significant difference in the clearance of tacrolimus.Conclusion:
Compared with using the sparse data only, the integrating modeling technique combining sparse data from the patients and dense data from the healthy volunteers improved the PopPK analysis of tacrolimus. 相似文献10.
Experimental pain research frequently relies on the recruitment of volunteers. However, because experimental pain research often involves unpleasant and painful sensations, it may be especially susceptible to sampling bias. That is, volunteers in experimental pain research might differ from nonvolunteers on several relevant variables that could affect the generalizability and external validity of the research. We conducted 2 studies to investigate potential sampling bias in experimental pain research. In study 1 we assessed participants' (N?=?275; age = 17–30 years) perceived likelihood of participating in pain research. Pain catastrophizing, fear of pain, illness and injury sensitivity, depression, anxiety, sensation-seeking, gender identity, body appreciation, and social desirability were also assessed as potential predictors of the likelihood to participate. In study 2, participants (N?=?87; Age = 18–31 years) could sign up for 2 nearly identical studies, with only one involving painful sensations. Thirty-six participants signed up for the pain study and 51 participants signed up for the no-pain study. Study 1 showed that lower levels of fear of pain, higher levels of sensation-seeking, and older age predicted the perceived likelihood of participating in pain research. Study 2 showed significantly higher levels of sensation-seeking in participants who signed up for the pain study compared with those who signed up for the no-pain study. The implications of these findings for future research, as well as the clinical conclusions on the basis of experimental pain research, are discussed.