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Effects of BG9928, an Adenosine A 1 Receptor Antagonist, in Patients With Congestive Heart Failure
Author(s) -
Gottlieb Stephen S.,
Ticho Barry,
Deykin Aaron,
Abraham William T.,
DeNofrio David,
Russell Stuart D.,
Chapman Douglas,
Smith William,
Goldman Steven,
Thomas Ignatius
Publication year - 2011
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270010375957
Subject(s) - medicine , natriuresis , placebo , heart failure , pharmacokinetics , tolerability , renal function , adenosine , pulmonary wedge pressure , adenosine receptor antagonist , anesthesia , adenosine receptor , pharmacology , adverse effect , receptor , alternative medicine , pathology , agonist
Previous studies suggest that adenosine A 1 receptor antagonists may promote natriuresis without deleterious effects on renal function. This study evaluated renal and hemodynamic effects as well as safety, pharmacokinetics, and tolerability of BG9928, a selective adenosine A 1 ‐receptor antagonist, in patients with heart failure. In this multicenter, randomized, double‐blind, placebo‐controlled, dose‐escalation study, 33 patients received a single dose of BG9928 (0.03, 0.3, 1.0, or 3.0 mg/kg) or placebo intravenously. Change from baseline in urinary sodium excretion for the 8‐hour postdose interval was greater for all dosing groups versus placebo. The 0.03‐mg/kg and 0.3‐mg/kg groups had significant reductions in body weight versus placebo (−0.8 kg, −1.1 kg, 0.3 kg, respectively; P < 005). No changes in creatinine clearance or hemodynamic parameters were observed among any of the BG9928 groups versus placebo. However, pulmonary capillary wedge pressure tended to decrease and correlated with weight loss. Across the range of doses studied, pharmacokinetic parameters were linear and predictable. One patient who received the highest dose (3.0 mg/kg) developed seizures, and no further patients received that dose. Single intravenous BG9928 doses of up to 1.0 mg/kg were well tolerated and increased sodium excretion without worsening renal function. Further studies are needed to determine the clinical benefit of adenosine A 1 receptor antagonism.