Effects of BG9928, an adenosine A1 receptor antagonist, in patients with congestive heart failure

Stephen S. Gottlieb, Barry Ticho, Aaron Deykin, William T. Abraham, David Denofrio, Stuart D. Russell, Douglas Chapman, William Smith, Steven Goldman, Ignatius Thomas

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)899-907
Number of pages9
JournalJournal of clinical pharmacology
Volume51
Issue number6
DOIs
StatePublished - Jun 1 2011

Fingerprint

Adenosine A1 Receptor Antagonists
Heart Failure
Placebos
Kidney
Pharmacokinetics
Hemodynamics
Sodium
Adenosine A1 Receptors
Natriuresis
Pulmonary Wedge Pressure
Adenosine
Weight Loss
Creatinine
Seizures
Body Weight
BG 9928
Safety

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Gottlieb, S. S., Ticho, B., Deykin, A., Abraham, W. T., Denofrio, D., Russell, S. D., ... Thomas, I. (2011). Effects of BG9928, an adenosine A1 receptor antagonist, in patients with congestive heart failure. Journal of clinical pharmacology, 51(6), 899-907. https://doi.org/10.1177/0091270010375957

Effects of BG9928, an adenosine A1 receptor antagonist, in patients with congestive heart failure. / Gottlieb, Stephen S.; Ticho, Barry; Deykin, Aaron; Abraham, William T.; Denofrio, David; Russell, Stuart D.; Chapman, Douglas; Smith, William; Goldman, Steven; Thomas, Ignatius.

In: Journal of clinical pharmacology, Vol. 51, No. 6, 01.06.2011, p. 899-907.

Research output: Contribution to journalArticle

Gottlieb, SS, Ticho, B, Deykin, A, Abraham, WT, Denofrio, D, Russell, SD, Chapman, D, Smith, W, Goldman, S & Thomas, I 2011, 'Effects of BG9928, an adenosine A1 receptor antagonist, in patients with congestive heart failure', Journal of clinical pharmacology, vol. 51, no. 6, pp. 899-907. https://doi.org/10.1177/0091270010375957
Gottlieb, Stephen S. ; Ticho, Barry ; Deykin, Aaron ; Abraham, William T. ; Denofrio, David ; Russell, Stuart D. ; Chapman, Douglas ; Smith, William ; Goldman, Steven ; Thomas, Ignatius. / Effects of BG9928, an adenosine A1 receptor antagonist, in patients with congestive heart failure. In: Journal of clinical pharmacology. 2011 ; Vol. 51, No. 6. pp. 899-907.
@article{82a1cd0fde4042d5b1444cdb924b7c58,
title = "Effects of BG9928, an adenosine A1 receptor antagonist, in patients with congestive heart failure",
abstract = "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.",
author = "Gottlieb, {Stephen S.} and Barry Ticho and Aaron Deykin and Abraham, {William T.} and David Denofrio and Russell, {Stuart D.} and Douglas Chapman and William Smith and Steven Goldman and Ignatius Thomas",
year = "2011",
month = "6",
day = "1",
doi = "10.1177/0091270010375957",
language = "English (US)",
volume = "51",
pages = "899--907",
journal = "Journal of Clinical Pharmacology",
issn = "0091-2700",
publisher = "SAGE Publications Inc.",
number = "6",

}

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 - 2011/6/1

Y1 - 2011/6/1

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.

UR - http://www.scopus.com/inward/record.url?scp=79955792526&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955792526&partnerID=8YFLogxK

U2 - 10.1177/0091270010375957

DO - 10.1177/0091270010375957

M3 - Article

C2 - 20926754

AN - SCOPUS:79955792526

VL - 51

SP - 899

EP - 907

JO - Journal of Clinical Pharmacology

JF - Journal of Clinical Pharmacology

SN - 0091-2700

IS - 6

ER -