Abstract:
AIM:Amiselimod (MT-1303) is a selective sphingosine 1-phosphate 1 (S1P1 ) receptor modulator which is currently being developed for the treatment of various autoimmune diseases. Unlike some other S1P receptor modulators, amiselimod seemed to show a favourable cardiac safety profile in preclinical, phase I and II studies. The aim of the current study was to characterize the cardiac effects of amiselimod by directly comparing it with fingolimod and placebo. METHODS:A total of 81 healthy subjects aged 18-55 years were equally randomized to receive amiselimod 0.4 mg, amiselimod 0.8 mg, placebo or fingolimod 0.5 mg once daily for 28 days. The chronotropic/dromotropic and inotropic effects were evaluated using intensive Holter electrocardiogram and echocardiography. RESULTS:Unlike fingolimod, neither amiselimod dose exerted acute (1-6 h) negative chronotropic effects on Days 1 and 2. The lowest nadir mean hourly heart rate was observed on Day 14 in the amiselimod 0.4 mg group (least squares mean difference: -4.40 bpm, 95% confidence interval -7.15, -1.66) and Day 7 in the 0.8 mg group [-3.85 bpm (-6.58, -1.11)] compared with placebo, but these changes were smaller than those with fingolimod on Day 1 [-6.49 bpm (-8.95, -4.02)]. No clinically significant bradyarrhythmia or cardiac functional abnormalities were observed in either amiselimod group. Both amiselimod doses were well tolerated and no serious adverse events were reported. Fingolimod was also generally well tolerated, although one subject was withdrawn owing to highly frequent 2:1 atrioventricular blocks on Day 1. CONCLUSION:The study demonstrated a more favourable cardiac safety profile for amiselimod than fingolimod when administered over 28 days in healthy subjects.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Harada T,Wilbraham D,de La Borderie G,Inoue S,Bush J,Camm AJdoi
10.1111/bcp.13203subject
Has Abstractpub_date
2017-05-01 00:00:00pages
1011-1027issue
5eissn
0306-5251issn
1365-2125journal_volume
83pub_type
杂志文章,随机对照试验abstract:AIMS:Since patients who regularly take NSAIDS may use sucralfate because of its cytoprotective properties, we examined the influence of this compound on the pharmacokinetics of diclofenac. METHODS:Potassium diclofenac (105 mg) was administered orally to eighteen healthy male volunteers with or without a 5-day pre-trea...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1997.tb00040.x
更新日期:1997-01-01 00:00:00
abstract::1 beta-adrenoceptor blockade with metoprolol provoked, both at rest and during exercise, a decrease of 'active' renin and angiotensin II together with an increase of 'inactive' renin and unchanged 'total' renin. The significant exercise-provoked increases in angiotensin II, plasma renin activity and 'active', 'inactiv...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1979.tb00918.x
更新日期:1979-02-01 00:00:00
abstract::Both the acute blood pressure lowering and renal effects of the calcium antagonist nicardipine and those after 1 week's treatment were investigated in 10 normotensive volunteers and in 10 patients with mild to moderate essential hypertension. After 1 week of placebo, nicardipine was administered orally for 1 week (20 ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb05022.x
更新日期:1984-07-01 00:00:00
abstract::1. To assess the risk of end-stage renal disease (ESRD) associated with the regular use of three classes of non-narcotic analgesics, we performed a case-control study of 340 patients with ESRD on a haemodialysis maintenance program and 673 hospital controls. 2. The overall odds ratio estimate for non-narcotic analgesi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb03841.x
更新日期:1990-11-01 00:00:00
abstract::Essential hypertension is an escalating problem for industrialized populations. It is currently seen as a 'complex' genetic trait caused by multiple susceptibility genes the effects of which are modulated by gene-environment and gene-gene interactions. Nevertheless, the success to date in identifying these susceptibil...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2125.2001.01254.x
更新日期:2001-01-01 00:00:00
abstract::1. In order to investigate accurately the biochemical effects of renin inhibition in man, we have developed a sensitive assay to measure angiotensin I (1-10) decapeptide. 2. Angiotensins were extracted from plasma by adsorption to phenylsilylsilica, and angiotensin I (Ang I) was quantified by radioimmunoassay. The det...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1992.tb04032.x
更新日期:1992-03-01 00:00:00
abstract:AIMS:This study assessed the effects of the CYP3A inhibitors lopinavir/ritonavir (LPV/r) on the steady-state pharmacokinetics (PK) of aplaviroc (APL), a CYP3A4 substrate, in healthy subjects. METHODS:In Part 1, APL PK was determined in eight subjects who received a single oral 50-mg APL test dose with/without a single...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2006.02661.x
更新日期:2006-09-01 00:00:00
abstract::The disposition and effect of orally administered prazosin have been studied in eight women with hypertension which was uncontrolled by beta-adrenoceptor blockade during the last trimester of pregnancy. Results were compared with healthy men of similar age. The median time to peak concentration was 165 min during preg...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb02213.x
更新日期:1983-11-01 00:00:00
abstract::1. We present a novel index for expressing the exposure of the infant to drugs in breast milk, which unifies two independent factors: a pharmacokinetic parameter, drug clearance, and a physiochemical parameter, i.e. milk-to-maternal plasma drug concentration ratio (M/P ratio). 2. During breast-feeding by a woman recei...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1994.tb04331.x
更新日期:1994-08-01 00:00:00
abstract:AIMS:To summarize and extend the main conclusions and recommendations relevant to drug management during acute kidney disease (AKD) as agreed at the 16th Acute Disease Quality Initiative (ADQI) consensus conference. METHODS:Using a modified Delphi method to achieve consensus, experts attending the 16th ADQI consensus ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13449
更新日期:2018-02-01 00:00:00
abstract::Little is known about the administration of direct-acting oral anticoagulants (DOACs) and the occurrence of alopecia. Our aim was to analyse the reports of alopecia following DOAC administration received until 2 May 2018 from VigiBase, the World Health Organization database. A descriptive analysis of age, sex, serious...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14221
更新日期:2020-08-01 00:00:00
abstract::1 The new converting enzyme inhibitor RHC 3659 was tested in 15 male volunteers. The study consisted of two parts: first, the ability of a single oral dose (5, 10, 20, 40 or 80 mg) to inhibit the pressor response to exogenous angiotensin I was tested with blood pressure and heart rate monitored continuously through an...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1981.tb01327.x
更新日期:1981-12-01 00:00:00
abstract:AIMS:Formoterol is a beta2-adrenoceptor agonist marketed as a racemic mixture of the active (R; R)- and inactive (S; S)-enantiomers (rac-formoterol). The drug produces prolonged bronchodilation by inhalation but there is significant interpatient variability in duration of effect. Previous work has shown that in humans ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2000.00133.x
更新日期:2000-02-01 00:00:00
abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:The dominant health economic units upon which new treatment funding decisions are made are the incremental cost per life year gained (LYG) or the cost per quality-adjusted life year (QALY) gained. Neither of these units modifies the amount of health gained, by the amount of heal...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2007.02996.x
更新日期:2008-02-01 00:00:00
abstract::Plasma melatonin was used to determine overall beta-adrenergic transmission through pineal neuro-effector junctions during desmethylimipramine (DMI) treatment in 10 normal subjects. Changes in plasma melatonin indicated that an initial increase in noradrenaline (NA) transmission produced by DMI was counteracted by ada...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb02717.x
更新日期:1985-06-01 00:00:00
abstract::Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions as a key regulator of cell growth, division and survival. Many haematologic malignancies exhibit elevated or aberrant mTOR activation, supporting the launch of numerous clinical trials aimed at evaluating the potential of single agent m...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12888
更新日期:2016-11-01 00:00:00
abstract::Eight healthy normal subjects (19-23 years) received graded intravenous isoprenaline infusions PRE- and POST-atropine, 0.04 mg/kg i.v. The adequacy of atropinization was tested with bolus intravenous injections of phenylephrine. PRE-atropine, isoprenaline caused an increase in heart rate and systolic pressure, but a d...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02469.x
更新日期:1984-09-01 00:00:00
abstract::Theophylline clearance was studied in normal healthy volunteers before and after chronic oral dosing. Oral theophylline clearance showed a significant decrease (P less than 0.001) from 59.3 +/- 6.48 ml/min (mean +/- s.e. mean, n = 10) to 48.0 +/- 6.4 ml/min. Steady-state intravenous clearance decreased by 26 +/- 2% fr...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02385.x
更新日期:1984-05-01 00:00:00
abstract:AIMS:To investigate uptake of fluconazole into the interstitial fluid of human subcutaneous tissue using the microdialysis and suction blister techniques. METHODS:A sterile microdialysis probe (CMA/60) was inserted subcutaneously into the upper arm of five healthy volunteers following an overnight fast. Blisters were ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2003.01930.x
更新日期:2003-11-01 00:00:00
abstract::Metabolomics is recognized as a powerful top-down system biological approach to understand genetic-environment-health paradigms paving new avenues to identify clinically relevant biomarkers. It is nowadays commonly used in clinical applications shedding new light on physiological regulatory processes of complex mammal...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2012.04216.x
更新日期:2013-03-01 00:00:00
abstract::The effect of urinary pH on flecainide excretion has been evaluated in six healthy subjects after a single oral dose of 300 mg flecainide administered as the acetate salt. The cumulative urinary excretion of unchanged flecainide under acidic conditions (134.0 +/- 16.1 mg; mean +/- s.e. mean) was significantly higher t...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02370.x
更新日期:1984-04-01 00:00:00
abstract::1. Alfuzosin is a post-synaptic alpha-adrenoceptor antagonist with antihypertensive and peripheral vasodilator properties. 2. We measured the effect of alfuzosin, 5 mg, on sympathetically-mediated venoconstriction by changes in the venous reflex response (VRR) in a randomised, double-blind, placebo-controlled, crossov...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1989.tb05330.x
更新日期:1989-01-01 00:00:00
abstract::1. N-hydroxylation is thought to be an essential step in the haemotoxicity of dapsone (DDS). To investigate both metabolism-dependent and cell-selective drug toxicity in vitro we have developed a three-compartment system in which an hepatic drug metabolizing system is contained within a central compartment separated b...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1993.tb05888.x
更新日期:1993-07-01 00:00:00
abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:• The topical second generation anti-histamine azelastine hydrochloride (AZE) and the potent corticosteroid fluticasone propionate (FP) are well established first-line treatments in allergic rhinitis (AR). • MP29-02, a novel intranasal AZE and FP formulation, has been shown to c...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2012.04222.x
更新日期:2012-07-01 00:00:00
abstract::Alpha 1-acid glycoprotein (AAG) concentrations and propranolol binding were investigated in the serum of elderly hospitalized patients with acute illness, and healthy elderly and young subjects. Significantly greater AAG concentrations and reduced unbound propranolol fraction were observed in the elderly with acute di...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02548.x
更新日期:1984-11-01 00:00:00
abstract::Ten healthy normal volunteers received an intravenous infusion of erythromycin lactobionate over 60 min to a total dose of 800 mg (n = 9), and 524 mg (n = 1). Blood samples were collected at 10 min intervals for 100 min and gastric contents aspirated, via a nasogastric tube, from pre-dose to 105 min after start of inf...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1986.tb05193.x
更新日期:1986-03-01 00:00:00
abstract:AIMS:Post licensing, the evaluation of drug safety relies heavily on the collation of sporadic, spontaneous reports on adverse effects. The aim was to assess the potential utility of a more systematic approach to the detection of adverse events that utilizes routinely collected clinical data from a large primary care p...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2008.03273.x
更新日期:2008-11-01 00:00:00
abstract::Small GTPases of the Rho family and their down-stream effectors Rho associated kinases (ROCKs) are the molecules that converge a spectrum of pathophysiological signals triggered by the diabetic milieu and represent promising molecular targets for nephroprotective treatment in diabetes. The review discusses recent stud...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12196
更新日期:2013-10-01 00:00:00
abstract:AIMS:Data regarding the cardiac toxicity of cabozantinib lacks. The aim of our study was to assess the risk of cabozantinib-related cardiotoxicity in mRCC patients. METHODS:We performed a multicentre prospective study on mRCC patients treated with cabozantinib between October 2016 and November 2017. Transthoracic echo...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/bcp.13895
更新日期:2019-06-01 00:00:00
abstract:AIM:The combination of ephedrine and caffeine has been used in herbal products for weight loss and athletic performance-enhancement, but the pharmacokinetic profiles of these compounds have not been well characterized. This study aimed to develop a mechanistic model describing ephedrine, norephedrine, and caffeine phar...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,meta分析
doi:10.1111/j.1365-2125.2005.02254.x
更新日期:2005-03-01 00:00:00