Abstract:
:Inclacumab is a novel monoclonal antibody directed against P-selectin in development for the prevention and treatment of atherosclerotic cardiovascular diseases. It is likely to be used concomitantly with heparin in patients undergoing percutaneous coronary intervention. Coadministration of both drugs may potentially increase the bleeding risk associated with heparin. This crossover study evaluated the potential pharmacodynamic interaction between inclacumab and unfractionated heparin in 18 healthy smokers. Owing to the long elimination of inclacumab (half-life of approximately 18 days), a 2-period, one-sequence study design was used. Subjects received an intravenous bolus injection of unfractionated heparin (5000 IU) on days 1 and 8 and an intravenous infusion of inclacumab (20 mg/kg) on day 8. Blood samples were collected on days 1 and 8 for pharmacodynamic effects of unfractionated heparin (anti-FXa and anti-FIIa activities, activated partial thromboplastin time and tissue factor pathway inhibitor) and over 6 months for pharmacokinetics of inclacumab. Sixteen subjects were eligible for pharmacodynamic analysis. Inclacumab had no clinically significant pharmacodynamic interaction with unfractionated heparin. With the exception of the minor but statistically significant increase of the maximum effect [Emax] of anti-FIIa activity, pharmacodynamic parameters (areas under the effect curve [AUElast] and Emax of anti-FXa) were almost similar on days 1 and 8. The 90% confidence intervals of geometric mean ratios of day 8 to day 1 for AUElast and Emax were however all contained within bioequivalence boundaries. The data demonstrate that the anticoagulant effect of unfractionated heparin was not affected by the administration of inclacumab.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Schmitt C,Mudie N,Ciorciaro C,Gaudreault Jdoi
10.1097/FJC.0000000000000211subject
Has Abstractpub_date
2015-04-01 00:00:00pages
386-92issue
4eissn
0160-2446issn
1533-4023journal_volume
65pub_type
杂志文章abstract::Recent evidence has shown that the kidneys produce and secrete a member of the atrial natriuretic peptide family, named urodilatin. This 32-amino acid peptide does not circulate in blood, but is secreted into urine. Urodilatin excretion closely parallels renal sodium excretion under various conditions that influence b...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-199322002-00028
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abstract::Prostaglandins (PG) E2, E2, E2 alpha, and I2 [prostacyclin (PGI2)] were tested in vitro on collateral arteries that enlarge following chronic occlusion of the femoral artery in the dog. After contraction with an ED50 dose of KCl, serial doses of a PG were added. Collateral arteries relaxed significantly to PGI2 (10(-7...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198209000-00014
更新日期:1982-09-01 00:00:00
abstract::The objective of this study was to characterize angiotensin II (AII) receptors in cerebral capillary endothelium and to examine whether the first step in AII responsiveness, namely AII receptor binding, is aberrant in cerebral microvessels obtained from adult spontaneously hypertensive rats (SHR). The binding of [3H]a...
journal_title:Journal of cardiovascular pharmacology
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doi:10.1097/00005344-198902000-00008
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abstract::After stroke-prone spontaneously hypertensive rats (SHRSP) received a salt-loaded diet to accelerate onset of stroke, the therapeutic effect of clentiazem, a benzothiazepine Ca antagonist, on neurologic and histologic disorders was examined. Treatment with clentiazem (3, 15, and 30 mg/kg) orally twice daily (b.i.d.) f...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199401000-00023
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abstract::The antihypertensive efficacy of the calcium entry blocker nitrendipine administered as monotherapy (20-80 mg; mean, 36/day) on the average for 144 days to 46 patients with essential hypertension (WHO I and II) was investigated in relation to age, pretreatment blood pressure, and plasma renin activity. In addition, we...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::Endothelial cell (EC) and vascular smooth muscle cell (VSMC) interactions play critical roles in restenosis following vascular injury. We examined the effects of intracellular iron chelation on endothelial cell cycle progression and VSMC modulation of endothelial cell growth. A diffusible, lipid-soluble iron chelator ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000159659.78675.4a
更新日期:2005-06-01 00:00:00
abstract::The antihypertensive effect of the combination of ketanserin, a new antiserotonergic agent, and thiazide has been evaluated in 35 patients with arterial hypertension of mild to moderate degree in the greater than 50-year-old age group. Twenty patients were given ketanserin (20 mg) + hydrochlorothiazide (25 mg) (treatm...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1987-01-01 00:00:00
abstract::The cardioprotective effects of bisoprolol were studied in a rat model of severe heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization, Lewis rats were divided into four groups: 0.1 mg/kg/day bisoprolol (Group 0.1), 1.0 mg/kg/day bisoprolol (Group 1) and 10 mg/kg/day bisoprolol (Group 1...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200110001-00012
更新日期:2001-10-01 00:00:00
abstract::The vasodilator action of organic nitrates can be severely impaired by induction of drug tolerance. A critical depletion of sulfhydryl groups has been proposed to play a key role in impairment of the biotransformation of organic nitrates to nitric oxide (NO). We studied the effects of the new cysteine-containing nitra...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199405000-00012
更新日期:1994-05-01 00:00:00
abstract::(+/-)-Dobutamine at concentrations < or =10(-5) M did not evoke contractions of rat gastric artery segments. However, when the tissues were contracted with methoxamine, (+/-)-dobutamine evoked concentration-dependent relaxation. The relaxant responses were not significantly affected by propranolol. In the same prepara...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199911000-00015
更新日期:1999-11-01 00:00:00
abstract::: Interstitial fibrosis is a common pathological change in various heart diseases, especially cardiac hypertrophy. Arginine vasopressin (AVP), one of the hallmarks of heart failure, exhibits a profibrotic effect by promoting the proliferation and differentiation of cardiac fibroblasts (CFs). In contrast, angiotensin-(...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000151
更新日期:2014-12-01 00:00:00
abstract::The effects of nitrendipine, a new antihypertensive agent, have been examined using the isolated rabbit aortic strip stimulated with either noradrenaline (1.7 X 10(-8) - 1.7 X 10(-5) mol/L) or potassium (22.7-52.7 mmol/L). Nifedipine, verapamil, phentolamine, papaverine, and minoxidil were used as reference compounds....
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1982-11-01 00:00:00
abstract::The binding characteristics and localization of bosentan, an orally active endothelin-1 (ET-1) antagonist, were studied on sections of human coronary artery by in vitro autoradiography. Competition studies were performed to determine the ability of bosentan to prevent [125I]ET-1 binding to the coronary vasculature. Th...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::Milrinone, a newly developed analogue of amrinone, possesses potent positive inotropic effects. Electrophysiologic actions of the drug have thus far been reported in only one study conducted on canine Purkinje fibers. The present study used microelectrode techniques to evaluate the electrophysiologic effects of milrin...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198503000-00021
更新日期:1985-03-01 00:00:00
abstract::We assessed whether local inhibition of myocardial converting enzyme by captopril and zofenopril reduces the functional and metabolic damage caused by ischemia and reperfusion. First we investigated the effects of zofenopril and captopril on the mechanical function, cellular redox state, and norepinephrine (NE) conten...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::Celiprolol is reported to be a new cardioselective beta blocker with novel ancillary properties including vasodilator effects. The purpose of this study was to investigate whether celiprolol possesses a direct vasodilatory effect on human vasculature in vivo and in vitro. We studied the in vivo effects of intra-arteri...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198711000-00015
更新日期:1987-11-01 00:00:00
abstract::The objective of this study was to investigate the cardioactive properties of oxybutynin, a drug that is widely prescribed for management of voiding dysfunction. Membrane currents were recorded from whole-cell-configured guinea pig ventricular myocytes, and action potentials were recorded from guinea pig and rabbit pa...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200002000-00024
更新日期:2000-02-01 00:00:00
abstract::beta-Adrenoceptor antagonists such as propranolol and atenolol ameliorate the symptoms of human hyperthyroidism. We wished to define whether the cardiac changes of hyperthyroidism are attenuated by treatment with the beta-adrenoceptor antagonist atenolol. Rats were treated with triiodothyronine (T3) [1 mg/kg/day subcu...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::Low doses of ethanol can produce negative functional effects in ventricular myocytes. This may be related to the nitric oxide-cyclic GMP signal transduction system. We tested the hypothesis that ethanol stimulated endothelial nitric oxide synthase and this caused the negative functional effects in cardiac myocytes. Th...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
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更新日期:2005-09-01 00:00:00
abstract::Intracellular [Ca2+]i overloading in cardiomyocytes is a fundamental pathogenic event associated with chronic aldosterone/salt treatment (ALDOST) and accounts for an induction of oxidative stress that leads to necrotic cell death and consequent myocardial scarring. This prooxidant response to Ca2+ overloading in cardi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3181cf0090
更新日期:2010-03-01 00:00:00
abstract::Endothelin-1 (ET-1) has been proven to activate two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Ca2+ channel (SOCC) in rabbit internal carotid artery vascular smooth muscle cells (ICA VSMCs). Ca2+ influx through these channels plays an essential role for ET-...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200208000-00016
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abstract::The combination of a beta-adrenoceptor-blocking drug with the dihydropyridine calcium channel antagonist, nitrendipine, has particular therapeutic advantages in the management of hypertension. The beta-blocker reduces any reflex increases in sympathetic nervous system and renin-angiotensin system activity that result ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198806124-00015
更新日期:1988-01-01 00:00:00
abstract::beta 2-Adrenoceptor function may be decreased in primary hypertension, resulting in increased peripheral resistance. To study the beta 2-adrenoceptor function, we used circulating mononuclear leukocytes (MNL) as a model system. Twenty untreated hypertensive subjects [(HT) 10 men and 10 women] and 20 age- and sex-match...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199311000-00004
更新日期:1993-11-01 00:00:00
abstract::This study evaluated the 24-h antihypertensive effect of single daily doses of celiprolol, a beta-1 adrenoceptor antagonist. Patients with supine diastolic BP between 95 and 114 mm Hg started on placebo or celiprolol 200 mg daily for 2 weeks; non-responders received 400 mg daily for 2 weeks and then 600 mg daily for a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-198608004-00027
更新日期:1986-01-01 00:00:00
abstract::Mikania laevigata, popularly known in Brazil as guaco, is widely used for respiratory disorders. As this plant is rich in coumarins, there is evidence of indications that it may cause bleeding and therefore should not be used concomitantly with anticoagulants. The basis of this information is very theoretical, with no...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000745
更新日期:2019-12-01 00:00:00
abstract::The effects of captopril on systolic function and diastolic myocardial expansion were assessed in an open-chest multiple occlusion model of myocardial stunning. Captopril was given as a 0.25 mg/kg bolus followed by a continuous infusion at 0.25 mg/kg/h for the duration of the stunning protocol, which was initiated 30 ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199304000-00008
更新日期:1993-04-01 00:00:00
abstract::Three-month-old spontaneously hypertensive rats were treated for 1, 2, or 3 months with daily intraperitoneal injections of naftidrofuryl (30 mg/kg). Systolic arterial pressure was measured. Tail arteries were removed and perfused at a constant flow rate of 2 ml/min. A concentration-response curve for serotonin was pr...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-01-01 00:00:00
abstract::The influence of intravenous diltiazem on hemodynamics and left ventricular function indices was studied in 14 patients with severe coronary artery disease at rest and during atrial pacing. We used a tip manometer catheter for recording left ventricular pressure tracings and a nuclear probe for measuring left ventricu...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199308000-00007
更新日期:1993-08-01 00:00:00
abstract::Atherosclerosis is an inflammatory response to accumulation of cholesterol in the artery wall. Low-density lipoproteins (LDL) accumulate and are oxidized to proinflammatory compounds in the arterial intima during hypercholesterolemia, leading to activation of endothelial cells, macrophages, and T cells. We sought to d...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318032aa11
更新日期:2007-04-01 00:00:00
abstract::The maximal increases in heart rate produced by intravenous xamoterol in anaesthetized cats and rats are less than that of (-)-isoprenaline. In cats, blood pressure was slightly raised, while in rats, supramaximal cardiac-stimulant doses produced reductions in blood pressure. In anaesthetized guinea pigs, cardiac-stim...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198603000-00014
更新日期:1986-03-01 00:00:00