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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Effects of BG9928, an adenosine A receptor antagonist, in patients with congestive heart failure.
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Effects of BG9928, an adenosine A receptor antagonist, in patients with congestive heart failure.

机译：腺苷A受体拮抗剂BG9928在充血性心力衰竭患者中的​​作用。

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摘要

Previous studies suggest that adenosine A 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-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 receptor antagonism.
机译：先前的研究表明，腺苷A受体拮抗剂可能会促进利尿，而不会对肾功能造成有害影响。这项研究评估了心力衰竭患者肾脏和血液动力学的影响，以及安全性，药代动力学和耐受性，一种选择性的腺苷A受体拮抗剂BG9928。在这项多中心，随机，双盲，安慰剂对照的剂量递增研究中，有33名患者接受了单剂量的BG9928（0.03、0.3、1.0或3.0 mg / kg）或安慰剂静脉注射。与安慰剂相比，所有给药组在给药后8小时间隔内尿钠排泄的基线变化均较大。 0.03 mg / kg和0.3-mg / kg组的体重较安慰剂显着降低（分别为-0.8 kg，-1.1 kg，0.3 kg; P <005）。与安慰剂相比，在任何BG9928组中均未观察到肌酐清除率或血液动力学参数的变化。然而，肺毛细血管楔形压力趋于降低并与体重减轻相关。在研究的剂量范围内，药代动力学参数是线性且可预测的。接受最高剂量（3.0 mg / kg）的一名患者出现癫痫发作，没有其他患者接受该剂量。高达1.0 mg / kg的单次静脉内BG9928剂量具有良好的耐受性，并且钠排泄量增加，而不会恶化肾功能。需要进一步的研究来确定腺苷A受体拮抗作用的临床益处。

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