TERBUTALINE INDUCED HYPOKALEMIA IN END STAGE RENAL DISEASE

高血钾是终末期肾病(ESRD)常见且危及生命的并发症。肾上腺素能受体(AR)激动剂常用于治疗高血钾。沙丁胺醇是一种常用的AR激动剂，可通过静脉输注或雾化吸入给药。沙丁胺醇给药后血钾浓度的峰值下降约为1mEq/L。然而，在终末期肾病患者中，沙丁胺醇给药有两个明显的问题。首先，响应的个体间变异性很高，导致峰值响应非常高，导致个体之间的峰值响应差异高达6倍。其次，20-40%的高钾血症和终末期肾病患者对-AR激动剂没有充分的反应(血钾峰值降低0.5mEq/L)。这种反应性变化的原因尚不清楚，但可能是由于药代动力学或药效学变化，或两者的组合。本研究的主要目的是利用药代动力学-药效学模型来建立特布他林引起的低钾血症(理想反应)和心动过速(不良反应)的量效关系。15名接受每周三次维持性血液透析的患者将接受7公斤特布他林皮下注射。特布他林浓度和反应测量(钾浓度和心率)将连续24小时获得。药代动力学和药效学模型将被用来建立浓度-效应关系。这些数据将使特布他林在高血钾和终末期肾病患者中的剂量策略得到改善。

Hyperkalemia is a common and life threatening complication of end-stage renal disease (ESRD). Adrenoceptor (AR) agonists are commonly used in the treatment of hyperkalemia. Albuterol is a commonly used AR agonist which is administered by intravenous infusion or via inhalation by a nebulizer. Peak reductions in plasma potassium concentration following administration of albuterol are approximately 1 mEq/L. However, two problems are apparent regarding albuterol administration in patients with ESRD. First, the interindividual variability in response is very high resulting in peak responses is very high resulting in peak responses varying by as much as six fold among individuals. Secondly, 20-40 percent of patients with hypekalemia and ESRD do not respone adequately (peak reduction in plasma potassium < 0.5 mEq/L) to -AR agonists. The reason for this variability in responsiveness is unknown but could be due to pharmacokinetic or pharmacodynamic variablility or a combination of both. The primary objective of this study is to use pharmacikinetic- pharmacodynamic modeling to develop terbutaline concentration-effect relationships for terbutaline- induced hypokalemia (desired response) and tachcardia (undesired response). Fifteen patients receiving thrice weekly maintenance hemodialysis will receive 7/kg of suboutaneous terbutaline. Terbutaline concentrations and response measurements (potassium concentrations and heart rate) will be obtained serially for 24 hours. Pharmacokinetic and pharmacodynamic models will be utilized to develop concentration-effect relationships. These data will allow for improved terbutaline dosing stategies in patients with hyperkalemia and ESRD.