BACKGROUND: Binodenoson, a highly selective agonist of the adenosine A 2A receptor, is being developed as a short-acting coronary vasodilator as an adjunct to radiotracers for use in myocardial stress imaging. This study was designed to assess the single-dose pharmacokinetics, safety, and tolerability of intravenous binodenoson. METHODS AND RESULTS: This was a single-center, open-label, nonrandomized, dose-escalation study in 24 healthy volunteers. Each subject received 3 successive intravenous doses of binodenoson (0.1, 0.2, 0.4, 0.6, 1, 2, 3, 4, 5, and 6 microg/kg), each infused over a period of 10 minutes and separated by washout periods of at least 120 minutes. Generally, binodenoson was well tolerated. There were no serious adverse events. However, there was a dose-related increase in adverse events (e.g., headache, nausea, vasodilation, chest pain), consistent with the pharmacology of the drug. Binodenoson exhibited linear pharmacokinetics as indicated by a dose-proportional increase in peak concentration (C max ) and area under the concentration-time curve (AUC). Systemic clearance was independent of dose but was correlated with body weight. The mean terminal half-life of binodenoson across all doses was 10 +/- 4 minutes. CONCLUSIONS: Overall, binodenoson was well tolerated and exhibited linear pharmacokinetics when administered intravenously over a 60-fold dose range from 0.1 to 6 microg/kg.