PII‐57

BACKGROUND/AIMS To investigate the PK of regadenoson, a selective A2A adenosine receptor agonist in subjects with renal dysfunction. METHODS Twenty‐four males and females were divided into four groups based on their creatinine clearance (CLCR) values. Serial plasma and urine drug concentrations were measured up to 36 hours after an iv bolus of 400 mcg regadenoson. Heart rate and hemodynamics were monitored for 24 hours. Plasma and urine concentration‐time data were modeled jointly using NONMEM. The influence of CLCR, body weight, body mass index, and age on model parameters was assessed. Heart rate values were compared to simulations based on previous knowledge of the effect of regadenoson on heart rate. RESULTS A 3‐compartment model including the effect of CLCR on regadenoson's renal clearance (renal clearance =SLOPE*CLCR) successfully described the PK of regadenoson. The non‐renal clearance and SLOPE were estimated to be 13.2 L/hr and 3.2. Central‐ and steady‐state volume of distributions were estimated to be 18 and 69 L. The distribution kinetics of regadenoson were not affected by renal function. Observed heart rates were consistent with the simulations. There were no serious adverse events in any subject. CONCLUSIONS PK of regadenoson was successfully described in subjects with different renal functions. Hemodynamic and adverse event assessments suggest that regadenoson is safe and well‐tolerated in these subjects. No dose adjustment is recommended for patients with impaired renal function. Clinical Pharmacology & Therapeutics (2005) 79 , P51–P51; doi: 10.1016/j.clpt.2005.12.182