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Phosphodiesterase Inhibitor

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6661. Interaction between the phosphodiesterase 5 inhibitor, tadalafil and 2 alpha-blockers, doxazosin and tamsulosin in healthy normotensive men. (Abstract)

Interaction between the phosphodiesterase 5 inhibitor, tadalafil and 2 alpha-blockers, doxazosin and tamsulosin in healthy normotensive men. Tadalafil, a phosphodiesterase type 5 inhibitor, is effective therapy for erectile dysfunction (ED). Men with ED have a high incidence of comorbid conditions including cardiovascular disease, diabetes mellitus and benign prostatic hyperplasia. Although phosphodiesterase type 5 inhibitors are safe when administered with most medications, sildenafil given

2004 The Journal of urology Controlled trial quality: uncertain

6662. Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension: a randomized prospective study. Full Text available with Trip Pro

Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension: a randomized prospective study. We sought to compare the short-term impact of three different phosphodiesterase-5 (PDE5) inhibitors on pulmonary and systemic hemodynamics and gas exchange parameters in patients with pulmonary arterial hypertension (PAH).The PDE5 inhibitor sildenafil has been reported to cause pulmonary vasodilation in patients (...) with PAH. Vardenafil and tadalafil are new PDE5 inhibitors, recently being approved for the treatment of erectile dysfunction.Sixty consecutive PAH patients (New York Heart Association functional class II to IV) who underwent right heart catheterization received short-term nitric oxide (NO) inhalation and were subsequently assigned to oral intake of 50 mg sildenafil (n = 19), 10 mg (n = 7) or 20 mg (n = 9) vardenafil, or 20 mg (n = 9), 40 mg (n = 8), or 60 mg (n = 8) tadalafil. Hemodynamics and changes

2004 Journal of the American College of Cardiology Controlled trial quality: uncertain

6663. Randomized trial of phosphodiesterase inhibitors versus catecholamines in patients with acutely decompensated heart failure. (Abstract)

Randomized trial of phosphodiesterase inhibitors versus catecholamines in patients with acutely decompensated heart failure. Increased neurohormone and cytokine concentrations are associated with adverse outcome in patients with congestive heart failure, so minimizing these increases may improve outcome, even in the acute phase of decompensated heart failure. The present study was designed to test the hypothesis that phosphodiesterase inhibitors, but not catecholamines, could favorably affect (...) neurohormone and cytokine profiles in patients with acutely decompensated heart failure. Twenty-nine patients underwent monitoring using a Swan-Ganz catheter and were randomly allocated to receive phosphodiesterase inhibitors (PDEI group, n=19) or catecholamines (CA group, n=10). Pulmonary capillary wedge pressure decreased significantly in both groups and cardiac output showed a slight, but not statistically significant increase, in both groups. There was a significant decrease in plasma brain natriuretic

2001 Japanese circulation journal Controlled trial quality: uncertain

6664. An overview of the pharmacokinetics of cilomilast (Ariflo), a new, orally active phosphodiesterase 4 inhibitor, in healthy young and elderly volunteers. (Abstract)

An overview of the pharmacokinetics of cilomilast (Ariflo), a new, orally active phosphodiesterase 4 inhibitor, in healthy young and elderly volunteers. The oral pharmacokinetics of cilomilast (Ariflo) were investigated in five separate studies in healthy volunteers. Cilomilast was rapidly absorbed, and pharmacokinetics were dose proportional after single and repeat dosing. The elimination half-life was 7 to 8 hours; accordingly, steady state was reached on the 3rd day of dosing. The degree

2001 Journal of clinical pharmacology Controlled trial quality: uncertain

6665. The new phosphodiesterase 4 inhibitor roflumilast is efficacious in exercise-induced asthma and leads to suppression of LPS-stimulated TNF-alpha ex vivo. (Abstract)

The new phosphodiesterase 4 inhibitor roflumilast is efficacious in exercise-induced asthma and leads to suppression of LPS-stimulated TNF-alpha ex vivo. Roflumilast is a new phosphodiesterase 4 (PDE4) inhibitor developed by Byk Gulden Pharmaceuticals for the treatment of chronic obstructive pulmonary disease and asthma. A placebo-controlled, randomized, double-blind, two-period crossover study was performed to investigate the safety and efficacy of roflumilast in 16 patients with exercise (...) of lipopolysaccharide (LPS)-stimulated tumor necrosis factor alpha (TNF-alpha) in whole blood ex vivo as a surrogate marker for the inhibition of inflammatory cell activation were taken predose on days 1 and 28. Serial safety measurements were performed during both study periods. Analysis of variance for the crossover design showed a significant superiority of roflumilast over placebo on day 28. The mean percentage fall of FEV1 after exercise was reduced by 41% as compared to placebo (p = 0.021). An improvement

2002 Journal of clinical pharmacology Controlled trial quality: uncertain

6666. The phosphodiesterase 4 inhibitor roflumilast is effective in the treatment of allergic rhinitis. (Abstract)

The phosphodiesterase 4 inhibitor roflumilast is effective in the treatment of allergic rhinitis. The beneficial effects of phosphodiesterase 4 (PDE4) inhibitors in allergic asthma have been shown in previous preclinical and clinical studies. Because allergic rhinitis and asthma share several epidemiologic and pathophysiologic factors, PDE4 inhibitors might also be effective in allergic rhinitis.The main objective of this study was to investigate the efficacy of oral roflumilast (500 microg/day (...) found for itching and rhinorrhea. With respect to the subjective obstruction score, a significant difference in comparison with placebo could be demonstrated within 4 days.This study shows that a PDE4 inhibitor, roflumilast, effectively controls symptoms of allergic rhinitis. Thus PDE4 inhibitors might be a future treatment option not only in allergic asthma but also in allergic rhinitis or the combination of the 2 diseases.

2001 The Journal of allergy and clinical immunology Controlled trial quality: uncertain

6667. A phosphodiesterase inhibitor, cilostazol, prevents the onset of silent brain infarction in Japanese subjects with Type II diabetes. Full Text available with Trip Pro

A phosphodiesterase inhibitor, cilostazol, prevents the onset of silent brain infarction in Japanese subjects with Type II diabetes. This study aimed to evaluate the effect of a phosphodiesterase inhibitor, cilostazol, on the prevention of silent brain infarction in diabetic patients without symptoms of vascular events.A total of 89 subjects were allocated at random to the cilostazol group ( n = 43) or the control group ( n = 46).After the study period (3.2 +/- 0.5 years), carotid intima-media

2002 Diabetologia Controlled trial quality: uncertain

6668. Use of near-infrared reflection spectroscopy to study the effects of X-ray contrast media on renal tolerance in rats: effects of a prostacyclin analogue and of phosphodiesterase inhibitors. (Abstract)

Use of near-infrared reflection spectroscopy to study the effects of X-ray contrast media on renal tolerance in rats: effects of a prostacyclin analogue and of phosphodiesterase inhibitors. Use of near-infrared reflection spectroscopy (NIR-RS) as a new model to assess renal tolerance of contrast agents and determination of the effects of a prostacyclin analogue and of two phosphodiesterase inhibitors on renal tolerance.NIR-RS was used to measure total hemoglobin, oxygenated hemoglobin (...) and tissue oxygen saturation in the renal cortex of rats and the effect of diatrizoate, iopromide and iotrolan injected at 1 g iodine/kg alone or together with the prostacyclin derivative, iloprost, or the phosphodiesterase inhibitors, rolipram and mesopram, on these parameters.Injection of the contrast media alone resulted in a 10% to 35% depression of total hemoglobin, oxygenated hemoglobin, and tissue oxygen saturation approximately 40 to 100 seconds after administration, whereas saline showed

2002 Investigative radiology Controlled trial quality: uncertain

6669. Pharmacokinetic and pharmacodynamic profile following oral administration of the phosphodiesterase (PDE)4 inhibitor V11294A in healthy volunteers. Full Text available with Trip Pro

Pharmacokinetic and pharmacodynamic profile following oral administration of the phosphodiesterase (PDE)4 inhibitor V11294A in healthy volunteers. To assess the pharmacokinetic and pharmacodynamic profile of the novel PDE4 inhibitor V11294A (3-(3-cyclopentyloxy-4-methoxybenzyl)-6-ethylamino-8-isopropyl-3H purine hydrochloride) in healthy male volunteers.This was a double-blind, single dose, randomized crossover study in eight healthy volunteers who received a single oral, fasting dose (...) Cmax (ng ml-1; mean +/- s.d.; 1398 +/- 298, 1000 +/- 400, respectively) after 2.63 +/- 0.79 and 5.9 +/- 2.3 h, respectively. For V11294A and V10332, t1/2 were 9.7 +/- 3.9 and 9.5 +/- 1.7 h, and AUC(0, infinity ) were 18100 +/- 6100 and 18600 +/- 8500 ng ml-1 h, respectively. At 3 h dosing, plasma concentrations of V11294A and V10332 (3-(3-cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl-3H-purin-6-ylamine) were 1300 +/- 330 and 860 +/- 300 ng ml-1, 7 and 3 times their in vitro IC50s for inhibition

2002 British journal of clinical pharmacology Controlled trial quality: uncertain

6670. The phosphodiesterase 5 inhibitor sildenafil has no effect on cerebral blood flow or blood velocity, but nevertheless induces headache in healthy subjects. Full Text available with Trip Pro

The phosphodiesterase 5 inhibitor sildenafil has no effect on cerebral blood flow or blood velocity, but nevertheless induces headache in healthy subjects. Cyclic nucleotides are important hemodynamic regulators in many tissues. Glyceryl trinitrate markedly dilates large cerebral arteries and increases cGMP. Here, the authors study the effect of sildenafil, a selective inhibitor of cGMP-hydrolyzing phosphodiesterase 5 on cerebral hemodynamics and headache induction. Ten healthy subjects were

2002 Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Controlled trial quality: uncertain

6671. Randomized comparison of the type 4 phosphodiesterase inhibitor cipamfylline cream, cream vehicle and hydrocortisone 17-butyrate cream for the treatment of atopic dermatitis. (Abstract)

Randomized comparison of the type 4 phosphodiesterase inhibitor cipamfylline cream, cream vehicle and hydrocortisone 17-butyrate cream for the treatment of atopic dermatitis. Therapeutic options to treat atopic dermatitis are limited. Leukocytes from atopic patients have an abnormally high activity of cyclic adenosine monophosphate (AMP)-phosphodiesterase (PDE), which can be normalized in vitro by PDE inhibitors. Cipamfylline is a new potent and selective inhibitor of PDE-4.To compare

2002 The British journal of dermatology Controlled trial quality: predicted high

6672. The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease. (Abstract)

The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease. The effect of vardenafil, a potent and highly selective phosphodiesterase-5 (PDE5) inhibitor, on symptom-limited exercise time, time to first awareness of angina, and time to ischemic threshold (ST-segment depression > or =1 mm from baseline) during exercise tolerance testing (ETT (...) ) was examined in patients with stable coronary artery disease (CAD).Erectile dysfunction (ED) is common among men with CAD. PDE5 inhibition is increasingly the preferred treatment option for ED. However, the effect of PDE5 inhibition on exercise-induced ischemia in CAD patients has received limited prospective evaluation.In this double-blind, crossover, single-dose multicenter study, 41 men with reproducible stable exertional angina due to ischemic CAD received vardenafil 10 mg or placebo, followed by ETT

2002 Journal of the American College of Cardiology Controlled trial quality: uncertain

6673. Does a single dose of the phosphodiesterase 4 inhibitor, cilomilast (15 mg), induce bronchodilation in patients with chronic obstructive pulmonary disease? (Abstract)

Does a single dose of the phosphodiesterase 4 inhibitor, cilomilast (15 mg), induce bronchodilation in patients with chronic obstructive pulmonary disease? Maintenance treatment with PDE(4) inhibitor cilomilast improves FEV(1) in chronic obstructive pulmonary disease (COPD) patients. We investigated the acute bronchodilating effects of a single dose of cilomilast with or without concomitant administration of inhaled salbutamol and/or ipratropium bromide in 21 patients with COPD (mean (SD) age

2003 Pulmonary Pharmacology & Therapeutics Controlled trial quality: uncertain

6674. Sustained efficacy and tolerability of vardenafil, a highly potent selective phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: results of a randomized, double-blind, 26-week placebo-controlled pivotal trial. (Abstract)

Sustained efficacy and tolerability of vardenafil, a highly potent selective phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: results of a randomized, double-blind, 26-week placebo-controlled pivotal trial. The durability of key efficacy response parameters and safety of vardenafil was evaluated in a pivotal trial conducted in a broad population of men with erectile dysfunction (ED) in North America. In this randomized, double-blind, placebo-controlled, multicenter, fixed

2003 Urology Controlled trial quality: uncertain

6675. Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study. (Abstract)

Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study. This study evaluated the efficacy and safety of vardenafil treatment for erectile dysfunction (ED) in men with diabetes.In this prospective multicenter double-blind placebo-controlled fixed-dose parallel-group phase III trial, 452 patients with diabetes (type 1 or type 2) and ED were randomized to take 10 or 20 mg

2003 Diabetes Care Controlled trial quality: uncertain

6676. Antiinflammatory effects of the phosphodiesterase-4 inhibitor cilomilast (Ariflo) in chronic obstructive pulmonary disease. Full Text available with Trip Pro

Antiinflammatory effects of the phosphodiesterase-4 inhibitor cilomilast (Ariflo) in chronic obstructive pulmonary disease. Cilomilast (Ariflo), a new oral phosphodiesterase-4 selective inhibitor, improves lung function in chronic obstructive pulmonary disease (COPD). We have evaluated its antiinflammatory effects in 59 patients with COPD randomized to receive cilomilast, 15 mg two times a day, or placebo for 12 weeks. Induced sputum differential cell counts were obtained at baseline (...) . Phosphodiesterase-4 inhibitors represent a promising new class of substances for use in antiinflammatory treatment of this disease.

2003 American journal of respiratory and critical care medicine Controlled trial quality: uncertain

6677. Therapeutic potential of a new phosphodiesterase inhibitor in acute lung injury. (Abstract)

Therapeutic potential of a new phosphodiesterase inhibitor in acute lung injury. The effects of LASSBio596, a phosphodiesterase type-4 and -5 inhibitor, were tested in Escherichia coli lipopolysaccharide (LPS)-induced acute lung injury. Twenty-four BALB/c mice were randomly divided into four groups. In the control group, saline (0.05 mL) was injected intratracheally (i.t.). The LPS group received LPS (10 microg i.t., 0.05 mL). In the LASSBio596 groups, LASSBio596 (10 mg x kg(-1), 0.2 mL (...) recruitment, TNF-alpha release, bronchoconstriction, alveolar collapse and the increment of collagen fibre content induced by LPS, independently of the moment of injection. In conclusion, LASSBio596 modulated the lung inflammatory process and had the potential to block fibroproliferation. Thus, agents that inhibit phosphodiesterase 4 and 5 simultaneously may be a useful adjunct therapy for acute lung injury.

2003 The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology Controlled trial quality: uncertain

6678. Effect of high-fat breakfast and moderate-fat evening meal on the pharmacokinetics of vardenafil, an oral phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction. (Abstract)

Effect of high-fat breakfast and moderate-fat evening meal on the pharmacokinetics of vardenafil, an oral phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction. The effects of food on the pharmacokinetics of vardenafil were examined in 25 healthy adult males. Single-dose vardenafil 20 mg was administered in a randomized four-way crossover design after an overnight fast (at 8 a.m.), after consumption of a high-fat breakfast (at 8 a.m.), on an empty stomach (at 6 p.m

2003 Journal of clinical pharmacology Controlled trial quality: uncertain

6679. Efficacy of the novel phosphodiesterase-4 inhibitor BAY 19-8004 on lung function and airway inflammation in asthma and chronic obstructive pulmonary disease (COPD). (Abstract)

Efficacy of the novel phosphodiesterase-4 inhibitor BAY 19-8004 on lung function and airway inflammation in asthma and chronic obstructive pulmonary disease (COPD). Selective inhibitors of phosphodiesterase-4 (PDE4) inhibit the hydrolysis of intracellular cAMP, which may result in bronchodilation and suppression of inflammation. We examined the effect of 1 week treatment with BAY 19-8004 (5 mg once daily), a novel orally administered PDE4 inhibitor, on trough FEV1 and markers of inflammation (...) % saline inhalation on the last day of treatment. FEV1 did not improve during either treatment in both patient groups (p>0.2). Sputum cell counts were not different following placebo and BAY 19-8004 treatment in asthma and COPD patients (p>0.2). However, only in patients with COPD, small but significant reductions in sputum levels of albumin and eosinophil cationic protein were observed (p<0.05). In conclusion, 1 week of treatment with the selective PDE4 inhibitor BAY 19-8004 does not affect FEV1

2003 Pulmonary Pharmacology & Therapeutics Controlled trial quality: uncertain

6680. The phosphodiesterase 3 inhibitor cilostazol dilates large cerebral arteries in humans without affecting regional cerebral blood flow. Full Text available with Trip Pro

The phosphodiesterase 3 inhibitor cilostazol dilates large cerebral arteries in humans without affecting regional cerebral blood flow. Cilostazol, an inhibitor of phosphodiesterase (PDE) type 3, is used clinically in peripheral artery disease. PDE3 inhibitors may be clinically useful in the treatment of delayed cerebral vasospasm after subarachnoid hemorrhage. The authors present the first results on the effect of cilostazol on cerebral hemodynamics in normal participants. In this double-blind

2004 Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Controlled trial quality: uncertain

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