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.
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