Safety and Tolerability of Neladenoson Bialanate, a Novel Oral Partial Adenosine A1 Receptor Agonist, in Patients With Chronic Heart Failure
| Autor: | Bernard Dorhout, Javed Butler, Savina Nodari, Piergiuseppe Agostoni, Jeroen J. Bax, Adriaan A. Voors, Raymond J. Kim, Michele Senni, Mihai Gheorghiade, Wilfried Dinh, Hans-Dirk Düngen, Piotr Ponikowski |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Agonist Cardiac function curve medicine.medical_specialty medicine.drug_class 030204 cardiovascular system & hematology Rolofylline 03 medical and health sciences chemistry.chemical_compound Adenosine A1 receptor 0302 clinical medicine Internal medicine Heart rate medicine Pharmacology (medical) Pharmacology Ejection fraction business.industry medicine.disease 030104 developmental biology chemistry Tolerability Heart failure Anesthesia Cardiology business |
| Zdroj: | The Journal of Clinical Pharmacology. 57:440-451 |
| ISSN: | 0091-2700 |
| Popis: | We studied safety and tolerability of neladenoson bialanate, a novel oral selective partial adenosine A1 receptor agonist that maintains the cardioprotective effects of adenosine without the undesired side effects of a full agonist, in 2 pilot studies in patients with heart failure with reduced ejection fraction (HFrEF). The β-blocker interaction study was a single-blind, placebo-controlled study on the effects of a 30-mg single dose of neladenoson bialanate on atrioventricular (AV) conduction in 11 patients with HFrEF treated with β-blockers. The PARSiFAL pilot study was a double-blind, placebo-controlled study on the effects of a 7-day treatment with 10 or 20 mg neladenoson bialanate or placebo in 31 patients with HFrEF on β-blocker therapy. In the β-blocker interaction study with 11 HFrEF patients, no second- or third-degree AV block was detected on 48-hour Holter monitoring. In the 31 HFrEF patients included in the PARSiFAL pilot study, no second- or third-degree AV blocks were observed during 24-hour Holter monitoring, and no effects were seen on heart rate and blood pressure. Median absolute changes in LVEF, measured by cardiac magnetic resonance, were 1.9% (interquartile range -1.1 to 4.3), 0.3% (-1.4 to 2.7), and 2.2% (0.4 to 4.5), in the placebo, 10-mg, and 20-mg groups, respectively. Treatment of HFrEF patients with the novel partial adenosine A1 agonist neladenoson bialanate appeared to be safe in 2 small pilot studies, and no atrioventricular conduction disorders or neurological side effects were observed. No significant early changes in cardiac function were detected. |
| Databáze: | OpenAIRE |
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