TY - JOUR
T1 - Effects of BG9928, an adenosine A1 receptor antagonist, in patients with congestive heart failure
AU - Gottlieb, Stephen S.
AU - Ticho, Barry
AU - Deykin, Aaron
AU - Abraham, William T.
AU - Denofrio, David
AU - Russell, Stuart D.
AU - Chapman, Douglas
AU - Smith, William
AU - Goldman, Steven
AU - Thomas, Ignatius
PY - 2011/6
Y1 - 2011/6
N2 - Previous studies suggest that adenosine A1 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 A1 receptor antagonism.
AB - Previous studies suggest that adenosine A1 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 A1 receptor antagonism.
KW - BG9928
KW - adenosine
KW - diuresis
KW - heart failure
KW - sodium
UR - http://www.scopus.com/inward/record.url?scp=79955792526&partnerID=8YFLogxK
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U2 - 10.1177/0091270010375957
DO - 10.1177/0091270010375957
M3 - Article
C2 - 20926754
AN - SCOPUS:79955792526
SN - 0091-2700
VL - 51
SP - 899
EP - 907
JO - Journal of clinical pharmacology
JF - Journal of clinical pharmacology
IS - 6
ER -