Abstract:
PURPOSE:This study was performed to determine the oral pharmacokinetics (PK) of EV-077 and its effects on pharmacodynamic (PD) markers. EV-077 blocks prostanoid-induced and isoprostane-induced cellular activation, and is in development for the treatment of vascular inflammation and associated complications of type-2 diabetes.. METHODS:This single-ascending-dose mono-centre study was randomised, placebo-controlled, and double-blinded within each dose group. Seven EV-077 doses were administered sequentially as an oral solution: 0.0125, 0.125, 0.375, 0.75, 1.25, 1.875 and 2.5 mg/kg body weight. PK, platelet aggregation, bleeding time and safety parameters were measured. Seven to eight healthy male subjects were dosed per group: five to six subjects received EV-077 and two subjects received placebo. RESULTS:Tmax was reached rapidly between 0.5 h and 1.0 h. Both Cmax and AUC increased linearly with the dose. The apparent terminal half-life (t½z) increased with the dose, most likely reflecting the increasing last quantifiable concentration with increasing dose; at 2.5 mg/kg, it was 2.7-6.9 h. Measurement of platelet aggregation showed no effect at 0.0125 mg/kg, and a full and reversible inhibition at doses of 0.125-2.5 mg/kg. The average bleeding time was dose-dependently prolonged, but was always below 9 min. The PK/PD profile showed that at plasma concentrations above 20 ng/ml, EV-077 platelet aggregation was completely inhibited (>90 %). All tested doses were well tolerated. CONCLUSIONS:Orally administered EV-077 was well tolerated, readily absorbed, reached Cmax within 1 h, with a linear PK based on Cmax and AUC. The inhibition of platelet aggregation was complete and reversible at doses of 0.125 mg/kg and higher, and average bleeding time was below 9 min.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Richardson A,Sakariassen KS,Meyer JP,Alberts P,Sorensen ASdoi
10.1007/s00228-012-1348-9subject
Has Abstractpub_date
2013-03-01 00:00:00pages
459-65issue
3eissn
0031-6970issn
1432-1041journal_volume
69pub_type
杂志文章,随机对照试验abstract::The aim of the study was to examine the effect of chronic angiotensin converting enzyme inhibition on haemodynamics and left ventricular performance during long-lasting exercise at the anaerobic threshold. For this purpose exercise haemodynamics and left ventricular performance were assessed in 14 physically trained h...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00194331
更新日期:1995-01-01 00:00:00
abstract::The pharmacokinetics of piretanide, a new loop diuretic, were studied in seven patients with severe liver disease before and after resolution of ascites. The time to maximum concentration was significantly prolonged by the presence of ascites. Tmax after relief of ascites was similar to that seen for normal volunteers...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00544070
更新日期:1985-01-01 00:00:00
abstract::The effect of long-term treatment on the absorption and disposition of metoprolol has been evaluated in 8 healthy, non-smoking, elderly individuals (mean age 74.5 years) and in a control group of 8 healthy, young individuals. Two trace doses of [3H]metoprolol were given i.v., first concomitantly with a single oral 50 ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00544048
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abstract:OBJECTIVE:Use of analgesic drugs in acute renal colic varies widely in different countries. In order to assess the prescribing patterns in acute renal colic in French emergency departments (EDs), the present study compared intentions of prescription, real prescription and evidence-based data in a sample of emergency pr...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s002280050574
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abstract:OBJECTIVE:To examine the association between the sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of lung cancer. METHOD:Meta-analysis of case-control studies using a random effects model. The "Main outcome measure" was the odds ratio for the risk of lung cancer, using extensive metabolisers as the ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,meta分析
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abstract::The Danish retail pharmacies' drug subsidy system is completely computerized. The data are person-identifiable, making it possible to chart the population's drug use from the perspective of individual users. We decided to explore the potential of this data source and to analyse heavy drug users specifically. The analy...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00191170
更新日期:1994-01-01 00:00:00
abstract::To evaluate the influence of the stomach and the cholinergic system on gallbladder contraction induced by physiological stimuli, the reduction in gallbladder volume in 7 healthy volunteers has been studied by real-time ultrasonography after the oral and intraduodenal administration of olive oil, preceded by pretreatme...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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更新日期:1990-01-01 00:00:00
abstract::Accidental intoxication with tramadol of a 6-month old infant was followed by severe cerebral depression. Studies on serum, cerebrospinal fluid, and urine drug levels indicated complete penetration of the blood-cerebrospinal fluid barrier by tramadol. ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00543498
更新日期:1984-01-01 00:00:00
abstract:OBJECTIVE:To describe the epidemiology of psychotropic drug use in a sample of Italian outpatient psychiatric services. METHODS:Drug-utilisation survey conducted within the framework of a broader prospective follow-up study with 67 Italian outpatient psychiatric services. RESULTS:The data concern 2322 patients recrui...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
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abstract:OBJECTIVE:The aim of the study was to determine the changes in consumption of psychotropic drugs by children aged less than 18 years during the years 1995 to 2001 in the Netherlands. METHODS:The year prevalence of antipsychotics, benzodiazepines, antidepressants and psychostimulants for boys and girls under 18 years w...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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abstract:PURPOSE:To investigate whether the CYP3A4*1G genetic polymorphism contributes to the variability in CYP3A activity and response to fentanyl. METHODS:One hundred and forty-three gynecologic patients who were scheduled to undergo abdominal total hysterectomy or myomectomy with general anesthesia were enrolled in this st...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:2010-01-01 00:00:00
abstract::A randomized multicentre between-patient study comparison has been made of the efficacy and tolerability of cadralazine and prazosin, both administered for 6 weeks to hypertensive patients with a supine diastolic blood pressure (DBP) greater than or equal to 95 mmHg whilst on a beta-adrenoceptor-blocker. The doses of ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/BF00315223
更新日期:1991-01-01 00:00:00
abstract::1. The effect of pre-dosing with 15 mg domperidone, a relatively selective dopamine 2-receptor antagonist, on the ocular hypotensive action of a single oral dose of 25 micrograms pergolide, a dopamine 2-receptor agonist, was studied in 9 normal human volunteers, using a non-invasive method. 2. Compared with domperidon...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF02336684
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abstract:PURPOSE:The population pharmacokinetics (PK) of lopinavir in tuberculosis (TB)/human immunodeficiency virus (HIV) co-infected South African children taking super-boosted lopinavir (lopinavir/ritonavir ratio 1:1) as part of antiretroviral treatment in the presence of rifampicin were compared with the population PK of lo...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-010-0847-9
更新日期:2010-10-01 00:00:00
abstract::A single dose of 60 mg trimetazidine (the normal daily dose) improved exercise capacity in angina pectoris, as reflected by an increase in the duration of exercise, total work performed, and improvement in ECG signs of ischaemia. All these effects occurred without any detectable chronotropic or vasomotor effect. The i...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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abstract::The benzamide-derivative moclobemide (Ro 11-1163) is a new short-acting, reversible MAO-inhibitor, preferentially affecting Type A MAO, which is, being developed as an antidepressant agent. The effect of moclobemide on heart rate, blood pressure, electrocardiographic and systolic time intervals was assessed in eight h...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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abstract::The debrisoquine hydroxylation phenotype was studied in 152 unselected healthy Tasmanian subjects, who were mostly Caucasians of British ancestry. Following a 10 mg oral dose of debrisoquine (D), the ratio of D/4-hydroxydebrisoquine excreted in 8-h urine (metabolic ratio, MR) was determined. MR values were bimodally d...
journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
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更新日期:2020-11-11 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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abstract::Twenty-nine cases of self-poisoning with antidepressants (amitriptyline, imipramine, clomipramine, maprotiline, doxepine, nortriptyline, opipramol) were examined by frequent observation of CNS effects, heart rate, blood pressure and standard ECG, 24h-ECG-monitoring, measurement of systolic time intervals, EEG recordin...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:1982-01-01 00:00:00
abstract:AIMS:The study aimed to identify and describe adverse drug reactions and adherence to clinical guidelines in patients receiving treatment for type 2 diabetes mellitus (T2DM) in Cameroon. METHODS:The method used was a cross-sectional study at a tertiary diabetes care service in Yaoundé, Cameroon. Adult T2DM patients at...
journal_title:European journal of clinical pharmacology
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更新日期:2020-11-01 00:00:00
abstract:BACKGROUND:Zolmitriptan is a 5HT(1B/1D) receptor agonist effective in the acute treatment of migraine. Clinical trials in the USA and Europe have demonstrated the optimal oral therapeutic dose to be 2.5 mg. The 2.5-mg oral tablet has recently been licensed in Japan. OBJECTIVE:To compare the pharmacokinetics of zolmitr...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:1990-01-01 00:00:00
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journal_title:European journal of clinical pharmacology
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更新日期:1990-01-01 00:00:00
abstract::7-3H-phenylephrine was given to 15 volunteers by a short-infusion n = 4) or p.o. (10 volunteers, 1 patient with porto-caval anastomosis). Analysis of serum for free 3H-phenylephrine and fractionation of urinary radioactivity was performed by ion-exchange and thin-layer chromatography. As almost the same 3H-activity wa...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:1982-01-01 00:00:00
abstract::The haemodynamic effects of intravenous metoprolol, over the dose-range 2.5--20 mg, were studied in 12 patients with coronary heart disease. The pharmacodynamic activity of the drug was confirmed by the suppression of exercise systolic pressure and tachycardia. There were statistically significant dose-response reduct...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:1981-01-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
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更新日期:2013-11-01 00:00:00