Abstract:
:The oral anticoagulant edoxaban, a factor Xa inhibitor, will likely be coadministered with digoxin in some patients with atrial fibrillation. Both drugs are substrates for P-glycoprotein. The objective of this phase 1, parallel study was to assess the effects of coadministration of both drugs on their respective pharmacokinetics (PK) and pharmacodynamics (PD). Forty-eight subjects, aged 18 to 45 years, received either edoxaban 60 mg once daily × 7 days (n = 24) or digoxin 0.25 mg twice daily × 2 days and once daily × 5 days (n = 24) and then concomitantly for 7 days. Serial blood and urine samples were collected for digoxin and edoxaban concentrations on days 7 and 14. Serial coagulation assays were measured for edoxaban on days 7 and 14. Edoxaban PK parameters demonstrated mild increases in area under the curve and peak concentrations of 9.5% and 15.6%, respectively, when coadministered with digoxin. Although digoxin PK parameters demonstrated increased area under the curve and peak concentrations of 8.3% and 28%, respectively, plasma concentrations were within the established therapeutic range. Edoxaban PD were consistent with PK. Both drugs were well tolerated alone or in combination. No clinically significant changes in PK, PD, or renal elimination were observed with concomitant administration of edoxaban and digoxin.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Mendell J,Noveck RJ,Shi Mdoi
10.1097/FJC.0b013e31826265b6.subject
Has Abstractpub_date
2012-10-01 00:00:00pages
335-41issue
4eissn
0160-2446issn
1533-4023pii
00005344-201210000-00002journal_volume
60pub_type
杂志文章,随机对照试验abstract::The effects of SIN-1 were studied on isolated aortic rings and perfused hindquarters of the rat and were compared with the effects of nitroglycerin and endothelium-derived relaxing factor (EDRF) released by acetylcholine or histamine (aorta) and carbachol (hindquarters). SIN-1 relaxes rat aortic rings in a dose-depend...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::This study investigated the role of perivascular adipose tissue (PVAT) in the beneficial effects of andrographolide on vascular reactivity in endotoxaemic rats. After being challenged by lipopolysaccharide (4 mg/kg intraperitoneally), the rats were treated with andrographolide (1 mg/kg intraperitoneally). The response...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31829497ea
更新日期:2013-08-01 00:00:00
abstract::This study examined whether the adenosine potentiator, 5-aminoimidazole-4-carboxamide riboside (AICAr), could limit tissue necrosis during acute myocardial infarction in rabbit hearts with minimal coronary collateral flow. Forty-four rabbits underwent 45 min of ischemia with or without coronary reperfusion for 180 min...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199201000-00010
更新日期:1992-01-01 00:00:00
abstract::We observed that heterozygous knockout (+/-, KO) of either endothelin-A- (ET(A)) or -B- (ET(B)) receptors significantly reduced the pressor responses to systemically administered endothelin-1 (ET-1) in ET(A) or ET(B) (+/-) KO mice when compared to wild-type (WT) mice (data not shown). Also, we observed that basal mean...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::Poor compliance may be responsible for symptomatic decompensation or neurohormonal "escape" in patients with heart failure treated over the long term with angiotensin-converting enzyme-1 (ACEI) drugs. Serum ACE activity is a poor index of neurohormonal suppression or haemodynamic effect after ACE-inhibitor treatment. ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-199701000-00018
更新日期:1997-01-01 00:00:00
abstract::In rats with deoxycorticosterone acetate (DOCA) salt hypertension, induction of diabetes with streptozotocin did not aggravate the elevation in blood pressure, but pressor and sympathetic nerve responses to electrical stimulation of the ventromedial hypothalamus were enhanced. Along with glycosuria and hyperglycemia, ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198211000-00026
更新日期:1982-11-01 00:00:00
abstract::The effects of tilisolol, a nonselective beta-adrenoceptor blocker, on transmembrane ionic currents were studied in single guinea pig ventricular myocytes by using the whole-cell voltage clamp technique. In the absence of beta-adrenergic stimulation, 10 microM tilisolol, a concentration higher than that used in the cl...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199705000-00005
更新日期:1997-05-01 00:00:00
abstract::Conflicting evidence has been reported on the hypothesis that vascular nitric oxide (NO) release is modulated by autonomic influences. Another controversial question is whether an insufficient degree of NO-dependent vasodilation may play a contributory role in the genesis of arterial hypertension. To address these que...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200111002-00006
更新日期:2001-11-01 00:00:00
abstract::We wished to determine the action of prostaglandins (PG) and to analyze pharmacologically the mechanisms of their action in isolated human uterine arteries in special reference to mediators liberated from the endothelium and subendothelial tissues. Helical strips of the human uterine artery with and without the endoth...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199508000-00021
更新日期:1995-08-01 00:00:00
abstract::This presentation has reviewed evidence from our laboratory that both structural and functional changes participate in the initiation and maintenance of hypertension in spontaneously hypertensive rats (SHR). Structural changes are present in the muscular arteries of the mesenteric and renal vasculature at 3- to 5-week...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198406004-00014
更新日期:1984-01-01 00:00:00
abstract::Adenosine A1 receptor (A1AR) activation contracts smooth muscle, although signaling mechanisms are not thoroughly understood. Activation of A1AR leads to metabolism of arachidonic acid, including the production of 20-hydroxyeicosatetraenoic acid (20-HETE) by cytochrome P4504a (CYP4a). The 20-HETE can activate protein ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3182919591
更新日期:2013-07-01 00:00:00
abstract::There is general agreement that the sympathetic nervous system is involved in the development of hypertension in spontaneously hypertensive rats (SHR). However, in a previous study we established that chronic administration of the selective alpha 1-adrenoceptor antagonist terazosin to SHR failed to prevent this phenom...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199305000-00015
更新日期:1993-05-01 00:00:00
abstract::Coronary artery disease is the most important cause of morbidity and mortality in Western countries. Its pathogenesis is unknown but involves an enhanced vasoconstriction and increased interaction of platelets and monocytes with the vessel wall, as well as proliferation, migration, and extracellular matrix formation o...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1994-01-01 00:00:00
abstract::We studied 12 patients receiving either chronic oral (p.o.) maintenance bretylium and/or acute intravenous (i.v.) bretylium to evaluate drug efficacy and pharmacokinetics. All patients were survivors of ventricular tachycardia or fibrillation. A new assay for bretylium was applied, and it proved sensitive and reliable...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198105000-00008
更新日期:1981-05-01 00:00:00
abstract::To determine whether the pattern of alcohol consumption, intake, and withdrawal modulates the incidence of malignant ventricular arrhythmias and sudden cardiac death due to beta-adrenergic stimulation in a species susceptible to administration of isoproterenol alone, a regimen was formulated in which both continuous a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198810000-00015
更新日期:1988-10-01 00:00:00
abstract::Estradiol may antagonize the adverse cardiovascular effects of angiotensin II (Ang II). We investigated the effects of 2-methoxyestradiol (2-ME), a nonestrogenic estradiol metabolite, on Ang II-induced cardiovascular and renal injury in male rats. First, we determined the effects of 2-ME on Ang II-induced acute change...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000649
更新日期:2019-03-01 00:00:00
abstract::The long-term efficacy of percutaneous transluminal coronary angioplasty (PTCA) is severely limited by the high incidence of vascular restenosis. Endothelin-1 (ET-1) has been implicated in the pathogenesis of this response, since circulating levels of this potent smooth-muscle mitogen are elevated after PTCA. Therefor...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199322008-00097
更新日期:1993-01-01 00:00:00
abstract::To assess the role of angiotensin II (AII) in development of myocardial injury during ischemia and reperfusion, the effects of short-term treatment with the angiotensin-converting enzyme (ACE) inhibitor lisinopril were compared with the effects of short-term treatment with L-158,338, an AII antagonist, in isolated wor...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199410000-00008
更新日期:1994-10-01 00:00:00
abstract::In primarily cultured pig coronary smooth muscle cells, extracellular adenosine triphosphate (ATP; 10(-9) to 10(-3) M) dose-dependently increases intracellular calcium ([Ca2+]i). The [Ca2+]i transients measured by fura-2 fluorescence consist of peak and plateau phases with [Ca2+]i values of 191.84 +/- 5.67 nM (n = 10)...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199905000-00019
更新日期:1999-05-01 00:00:00
abstract::To investigate the pathophysiologic role(s) of endothelin-1 (ET-1) in pulmonary hypertension, we studied the expression of ETB-receptor mRNA in the lung and venous plasma concentrations of ET-1 in rats with monocrotaline-induced pulmonary hypertension (PH). Three weeks after s.c. injection of monocrotaline (60 mg/kg),...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199322008-00088
更新日期:1993-01-01 00:00:00
abstract::Endothelial dysfunction is the pathophysiologic principle involved in the initiation and progression of arteriosclerosis, thus endothelial function serves as a "barometer" for cardiovascular health that can be used for the evaluation of new therapeutic strategies. This review provides an introduction to the concept of...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-200606001-00007
更新日期:2006-01-01 00:00:00
abstract::We studied the hemodynamic effects of four doses of milrinone, administered by intravenous (i.v.) infusion alone and after autonomic blockade with prazosin, propranolol, atropine, and clonidine. Plasma concentrations of milrinone (50-600 ng/ml) were similar to those used for the treatment of cardiac failure and were u...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198705000-00002
更新日期:1987-05-01 00:00:00
abstract::The effect of canrenone, an antialdosterone and partial ouabain-agonist drug, was studied in rats that developed volume expansion and hypertension after renal mass reduction and excess Na+ intake (RRM-salt). The RRM-salt was characterized by: (1) increased endogenous "digitalis-like" compounds in plasma [cross reactiv...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198801000-00012
更新日期:1988-01-01 00:00:00
abstract::The in vivo effects of two unsurmountable angiotensin II type 1 (AT1) antagonists, irbesartan (150 mg) and candesartan (8 mg), were studied in a double-blind, randomized, crossover study in 18 healthy men. The drugs' direct vascular effects were assessed as the rightward shift (dose ratio - 1) of angiotensin dose-effe...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-200204000-00012
更新日期:2002-04-01 00:00:00
abstract::The vasoconstrictor effects of endothelin-1 (ET-1) and norepinephrine (NE) were compared in the exteriorized rat mesentery in situ. ET-1 was 1,000 times more potent than NE in constricting both arterioles and venules. Vasoconstrictions induced by ET-1 lasted much longer than those caused by the catecholamine. At nonre...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198900135-00056
更新日期:1989-01-01 00:00:00
abstract::Endothelin-1 (ET-1) is synthesized and secreted by cardiomyocytes and induces cardiac hypertrophy. Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a lipid-activated nuclear receptor that negatively regulates the vascular inflammatory gene response by interacting with transcription factors, such as nuc...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000166303.33313.01
更新日期:2004-11-01 00:00:00
abstract::The understanding of blood pressure (BP) and heart rate (HR) variation, circadian changes, and the responses to nonclinical situations has been improved by automated ambulatory recordings. The antihypertensive efficacy of a once-daily regimen (10/20 mg) of nitrendipine was evaluated in detail using the lightest availa...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::In the initial seconds after a sudden reduction in coronary blood flow, a temporary mismatch between myocardial energy demand and supply exists. The mechanisms underlying the rapidly ensuing reduction in contractile function in the ischemic myocardium are still unknown. In the presence of some residual blood flow, a s...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1992-01-01 00:00:00
abstract::We previously showed that rat and cow blood vessels contain arginine vasopressin (AVP) of local origin. In the present study, to investigate potential roles for this locally produced peptide, we examined the effects of AVP on growth of cultured vascular endothelial and smooth muscle cells (EC, SMC). Treatment of cultu...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199503000-00004
更新日期:1995-03-01 00:00:00
abstract::We examined whether the activation of the renin-angiotensin system after intramuscular isoprenaline injection contributes to the simultaneous increase in vasopressin release. Plasma concentrations of vasopressin and angiotensin II were measured in conscious rats using specific radioimmunoassays. Intravenous infusions ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198011000-00010
更新日期:1980-11-01 00:00:00